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Uterine 


AND 


Tubal  Gestation 


A  STUDY  OF  THE   EMBEDDING   AND    DEVELOPMENT  OF  THE    HUMAN 

OVUM,    THE    EARLY   GROWTH    OF    THE    EMBRYO,    AND 

THE    DEVELOPMENT   OF   THE    SYNCYTIUM 

AND    PLACENTAL    GLAND 


BY 


SAMUEL    WYLLIS    BANDLER,    M.D. 

Instructor  in  Gynecology,  N.  Y.  Post-Graduate  Medical  School 


ILLUSTRATED    BY    NINETY-THREE    DRAWINGS 


Dr.  Francis  Huber 

209  E.  17th  St. 

N.  Y.  City 


NEW  YORK 

WILLIAM   WOOD   &   COMPANY 

MDCCCCIII 


Copyrighted,  1903, 

BY 

SAMUEL  WYLLIS  HANDLER. 


PRESS  OF 

Stettiner  Brothers, 

62-58  Duane  St., 

NEW  YORK. 


dedicated  to 
FERDINAND  GRAF  von  SPEE, 

PBOFESSOK    OF   ANATOMY    IN    THE    UNIVERSITY    OF    KIEL., 

IN   ADMIRATION    OF   HIS    MOST   VALUABLE   CONTRIBUTIONS   TO    OUR    SCIENTIFIC 
KNOWLEDGE  AND  IN  GRATITUDE  FOR  PERSONAL  KINDNESSES. 


PREFACE. 


Many  of  these  pages  appeared  in  The  American  Journal  op 
Obstetrics  and  Gynecology  under  the  title,  ' '  On  the  Etiology, 
Histology,  and  Usual  Course  of  Ectopic  Gestation."  Enough 
has  been  added  to  make  the  processes  antedating  and  accompany- 
ing uterine  gestation  fairly  complete  and  up  to  date.  The  es- 
sential features  in  this  channel,  as  regards  the  earliest  stages,  are 
to  be  credited  to  Spee.  Attempt  has  been  made  to  aid  in  the 
decision  concerning  several  doubtful  problems,  particularly  as 
to  the  origin  of  the  syncytium.  Attention  has  been  paid  to  the 
decided  probability  that  the  placenta  is  a  gland  with  potentials 
of  great  importance  from  the  standpoint  of  secretion.  Some 
personal  views  concerning  the  formation  of  villi  and  the  blood- 
forming  function  of  the  trophoblast  have  been  brought  forward 
with  a  full  realization  that  criticism  and  further  observations 
are  to  prove  them  correct  or  otherwise.  In  spite  of  the  great 
labors  of  gifted  investigators,  final  decision  is  yet  to  be  given  on 
many  points,  so  changeable  are  the  processes  at  various  stages 
and  so  probable  is  it  that  many  ova  are  pathological. 

To  Minot,  Mall,  v.  Spee,  and  others  we  are  greatly  indebted 
for  pioneer  work  on  allied  questions.  The  subject  of  chorioma, 
or  chorio-epithelioma,  has  been  introduced,  because  in  its  micro- 
scopical character  it  so  closely  reproduces  many  normal  condi- 
tions. 

I  am  under  great  personal  obligation  to  Dr.  A.  Brothers  for  the 
gross  specimens  which  furnished  the  material  for  Part  II  and  a 
portion  of  Part  III.  He  placed  all  of  his  large  material  and  his- 
tories at  my  disposal,  for  which  kindnesses  I  here  express  my  sin- 
cerest  thanks. 

Samuel  Wyllis  Bandler. 


CONTENTS. 


PART  I. 


THE  ESSENTIALS   OF   UTEKINE   GESTATION. 
CHAP.  PA«E. 

I.  The  Processes  Antedating  Uterine  Gestation 1 

A.  The  Trophic  Influence  of  the  Ovary 1 

B.  Constitutional  Changes  Dependent  on  the  Ovary 6 

C.  Menstruation    9 

D.  The  Action  of  Ovarian  Secretion  on  the  Endometrium.  12 

E.  The  Relation  of  Ovulation  and  Menstruation 13 

F.  Ovulation    15 

II.  The  Embedding  of  the  Ovum  in  the  Guinea-Pig 18 

A.  Uterus  of  the  Guinea-Pig 18 

B.  The  Embedding  of  the  Guinea-Pig's  Ovum 20 

III.  The  Embedding  of  the  Human  Ovum 32 

A.  The  Uterus  32 

Decidua  Menstrualis   33 

Decidua  Graviditatis  in  the  First  Week 33 

Decidua  Graviditatis   35 

B.  The  Embedding  of  the  Human  Ovum 37 

Ovum  in  the  Earliest  Stages 38 

Capsularis    39 

The  Enveloping  Zone 39 

IV.  The  Early  Development  of  the  Human  Ovum 40 

Division  into  Embryonal  and  Extra-Embyronal  Areas 15 

V.  The  Trophoblast  in  the  Ova  of  Animals 46 

The  Earliest  Development  of  the  Ectoblastic  Extra-Embry- 
onal Area  46 

VI.  The  Trophoblast  of  the  Human  Ovum 50 

The  Earliest  Development  of  the  Ectoblastic  Extra-Embry- 
onal Area  of  the  Ovum 50 

Trophoblast 50 

The  Primary  Intervillous  Space 53 

VII.  The  Further  Development  of  the  Human  Ovum 57 

The  Early  Development  of  the  Embryonal  Area 57 

VIII.  The  Chorionic  Villi 66 

A.  Early  Development    66 

B.  In  the  Fourth  Week  of  Uterine  Gestation 68 

IX.  The  Membrana  Chorii 75 

X.  The  Blood-Forming  Function  of  the  Trophoblast 82 

XI.  The  Further  Development  of  the  Uterine  Placenta 89 


Vlll  CONTENTS. 

CHAP.  •  PAGE. 

XII.  The  Placenta    93 

XIII.  The  Umbilical  Vessels  and  Cord 99 

A.  The   Umbilical   Vessels 99 

B.  The  Umbilical   Cord 101 

C.  The  Amnion   102 

XIV.  Gross  Anatomy  of  the  Placenta 103 

PART  II. 

THE  ESSENTIALS  OF  TUBAL  GESTATION. 

I.  Processes  Antedating  Gestation  in  the  Tube 109 

Etiology    109 

II.  Varying  Views  Concerning  the  Histology  of  Tubal  Gestation.  114 

The  Decidua 114 

Embedding  of  the  Ovum,  the  Reflexa  or  Capsularis 115 

Intervillous  Space    115 

Villi 116 

Deportation   . . .  117 

Conclusions     119 

III.  Embedding  of  the  Ovum  and  the  Development  of  Extra-Em- 

bryonal structures   121 

I.  The  Columnar  Type  of  Tubal  Gestation 121 

II.  The  Intercolumnar  Type  of  Tubal  Gestation 127 

III.  The  Centrifugal  Type  of  Tubal  Gestation 131 

Conclusions   135 

IV.  The  Usual  Course  of  Tubal  Gestation 137 

PART  III. 

OVARIAN   AND   PLACENTAL   SECRETION. 

The  Relation  of  the  Chorionic  Epithelium  to  Chorio-Epithe- 

lioma    145 

Chorio-Epithelioma  or  Chorioma 151 


LIST  OF  ILLUSTRATIONS 


embedding  of  guinea-pig's  ovum. 
Fig.  page. 

1.  Uterine  horn  ( Spee) 18 

2.  Compact  zone  of  uterine  lining  (Spee) 19 

3.  Ovum  free  in  uterine  cavity  ( Spee) 20 

3a.  Ovum  adherent  to  uterine  epithelium    (Spee) 21 

4.  Ovum  partially  embedded    ( Spee) 22 

5.  Further  stage  of  embedding  (Spee) 23 

6.  Partially  embedded  ovum  ( Spee) 24 

7.  Ovum  surrounded  by  symplasma  ( Spee) 25 

8.  Almost  embedded  ovum   ( Spee) 26 

9.  Ovum  entirely  under  uterine  epithelium  (Spee) 27 

10.  Demarkation  of  symplasma  (Spee) 28 

11.  Embedded  ovum    ( Spee) 29 

12.  Completely  embedded,  growing  ovum  (Spee) 30 

13.  Rapidly-growing  ovum    (Spee) 32 

EMBEDDING  OE   HUMAN  OVUM. 

14.  Menstrual  decidua  (Abel) 34 

14c.  Decidua  in  the  second  month  (Abel) 35 

146.  Gland  in  the  decidua  graviditatis 36 

15.  Schematic;  embedding  human  ovum  (Peters) 37 

16.  Schematic;  embedded  human  ovum  (Peters) 38 

THE   EARLY    DEVELOPMENT    OF    THE    HUMAN    OVUM. 

17.  Schematic;  ovum  with  ectoblast  and  entoblast 40 

17c.  Schematic ;  ovum  with  amnion 40 

176.  Schematic;   ovum  with  separating  amnion 41 

17c.  Schematic;   ovum  with  ectoblast,  entoblast,  amnion,  germinal 

plate,  but  no  mesoblast 41 

18.  Schematic;  ovum  with  beginning  growth  of  mesoblast 42 

18c.  Schematic;  ovum  with  three  germinal  layers 42 

19.  Ovum  with  three  germinal  layers  ( Peters) 43 

19c.  Schematic;  ovum  with  mesoblastic  periembryonal  slit 45 

HUMAN  TROPHOBLAST. 

20.  Trophoblast,  etc.,  of  three-day  ovum  (Peters) 50 

21.  Central  portion  of  trophoblast  layer  (Peters) 51 

22.  Trophoblast  infiltrated  with  blood  lacunse  (Peters) 52 

23.  Change  of  trophoblast  to  syncytium  (Peters) 53 

24.  Scheme  of  earliest  stage  of  placenta  (Peters) 54 


X  LIST   OF   ILLUSTRATIONS. 

EARLY  DEVELOPMENT  OF  THE  EMBRYONAL  AREA. 

PAGE 

25.  Ovum  v.  H.  of  Spee 57 

26.  Longitudinal  section  through  25 5& 

27.  Fig.  26  enlarged 58 

28.  Germinal  plate  of  ovum  v.  H.  of  Spee 59 

29.  Ventral  curve  in  the  germinal  plate . .  69 

29a.  Embryo  Gle  of  Spee 60 

296.  Embryo  Gle  of  Spee 61 

30.  Three  layers  of  a  human  embryo  (Keibel) 62 

30a.  The  forming  of  the  intestine  (Kollman) 63 

30o.  Human  embryo  2-4  mm.  long  (His) 63 

30c.  Caudal  end  of  embryo  3  mm.  long  (Keibel) 64 

30a.  Schematic;  embryo  with  ventral  surface  toward  the  abdominal 

pedicle   64 

30e.  Schematic;  embryonal  formation  (Waldeyer) 65 

THE  CHORIONIC  VILLI. 

31.  Schematic;  later  stage  of  placental  development  (Peters) 67 

31a.  A  well-developed  villus 68 

31&.  An  outgrowth  on  the  membrana  chorii 69 

32.  Villus  composed  of  trophoblast  cells 70 

32a.  Villus  with  protoplasmatic  trophoblast  cells 70 

33.  Villus  with  beginning  centre  of  mesoderm 71 

34.  Older  villus 71 

35.  Villus  in  various  stages 72 

35a.  Cell  group  with  invading  syncytium 72 

35&.  Further  stage  of  35a 73 

35c.  Further  stage  of  35& 73 

MEMBRANA   CHORII. 

36.  Membrana  chorii  of  five-weeks  ovum 78 

37.  Vacuoles  in  membrana  chorii 79 

38.  Membrana  chorii  of  tubal  ovum 85 

FURTHER  DEVELOPMENT  OF  UTERINE  PLACENTA. 

39.  Uterus  and  fetal  sac  of  seventh  week 89 

40.  Decidua  vera  90 

41.  Cell  groups  invading  the  serotina 91 

42.  Syncytial  cells  invading  the  serotina 91 

THE   PLACENTA. 

43.  Uterus  and  placenta  at  full  term 95 

44.  Utero-placenta  junction  at  full  term 95 

45.  Invading  fetal  cells 96 

46.  Placental  villi   96 


LIST   OF    ILLUSTRATIONS.  XI 

THE  UMBILICAL  VESSELS  AND  COED. 

PAGE. 

46a.  Young  embryo,  with  amnion 101 

466.  Schematic;    umbilical  cord 102 

46c.  Scheme  of  placenta 104 

PART  II. 

47.  Columnar  type  of  tubal  gestation 121 

47a.  Ovum  47,  magnified 122 

48.  Tubal  ovum  47 123 

49.  A  more  peripheral  section  of  47 123 

50.  A  still  more  peripheral  section  of  47 124 

51.  Most  peripheral  section  of  4  7 125 

52.  Change  of  trophoblast  to  syncytium 126 

53.  Inter  columnar  Type  of  Tubal  Gestation 127 

54.  Serotinal  area  of  53 128 

54a.  Typical  area  of  54 128 

55.  Serotinal  area  of  53 129 

55a.  Area  of  Fig.  55 130 

56.  Tubal   gestation   sac   with   fetus — Centrifugal   Type   of   Tubal 

Gestation    131 

56a.  Tubal  ovum  with  capsularis 132 

57.  Capsularis  and  tube  wall  of  56a 133 

58.  Advancing  trophoblast  cells  of  57 134 

59.  Serotinal  area  of  56a 135 

PART  III. 

CHOEIOMA. 

60.  Typical  form  of  chorioma 152 

61.  Fig.  60  magnified 153 

62.  Fig.  61  magnified 154 

63.  Fig.  60  magnified 155 

64.  Atypical  form  of  chorioma 156 


PART  I. 

THE  ESSENTIALS  OP  UTERINE  GESTATION. 


CHAPTER  I. 

THE    PROCESSES    ANTEDATING   UTERINE  . 
GESTATION. 

A.    THE    TROPHIC    INFLUENCE    OF    THE   OVARY. 

Halban  transplanted  the  ovaries  in  newly  born  guinea-pigs 
to  see  what  effect  transplantation  and  castration  would  exert 
upon  the  development  of  the  genitalia  and  the  breasts.  The 
comparisons  with  non-castrated  animals  are  very  interesting. 
In  the  castrated  guinea-pig  the  breasts  were  later  found  to  be 
one-fourth  the  normal  size;  the  genitalia  were  small,  the  vulva 
was  one-third  smaller  than  normal ;  the  uterus  was  as  small  as  at 
birth,  showing  very  slight  development  of  muscle  and  endo- 
metrium, and  containing  no  ciliated  cells.  The  breasts  showed 
no  glandular  tissue,  the  mammilla?  were  hypoplastic,  the  vaginal 
mucous  membrane  showed  both  squamous  and  cylindrical  epithe- 
lium— a  novel  condition.  When  the  ovaries  were  transplanted 
under  the  skin,  the  uterus  was  well  developed,  the  tubes  were 
normal,  the  vulva  was  large,  as  were  the  mammillae  likewise.  In 
the  transplantation  of  one  ovary  a  part  of  the  uterus  and  a  piece 
of  the  tube  had  likewise  been  taken,  and  these  grew  in  a  normal 
manner,  and  increased  in  size.  The  transplanted  piece  of  uterus 
contained  well-developed  muscle  and  normally  secreting  glands. 
The  portion  of  tube  showed  muscle,  epithelium,  and  ciliated  cells. 
Halban  thus  showed  the  influence  of  the  ovary,  as  a  secreting 
organ,  upon  the  uterus,  vagina,  vulva,  and  mamma.  He  con- 
siders it  probable  that  the  ovarian  secretion  acts  upon  the  uterus ; 
the  uterine  secretion  acting  in  turn  upon  the  mammary  gland. 

Ribbert  implanted  the  mamma  of  a  young  guinea-pig,  with  its 
covering  of  skin,  into  a  cut  near  the  ear.  The  wound  healed,  and 
five  months  after  the  operation,  the  animal  having  borne  two 
young,  this  mamma  secreted  milk  normally,  a  proof  that  the 
connection  between  the  breasts  and  the  ovary  and  uterus  is  to  be 
found  in  no  other  channels  than  those  of  the  circulation. 

Hegar  and  Kehrer  showed  that  in  newly-born  animals,  after 
castration,  the  uterus  does  not  develop,  but  remains  at  the  same 
stage,  or  even  undergoes  atrophy, 
l 


2  THE   PROCESSES    ANTEDATING    UTERINE    GESTATION. 

Sokoloff  castrated  rabbits  and  dogs  and  found  that,  a  short 
time  after,  they  became  fat  and  apathetic,  and  grew  constantly 
worse.  Subsequent  examination  of  the  uterus  divulged  muscular 
atrophy,  especially  of  the  circular  layer ;  the  vessels  were  fewer, 
the  walls  thicker,  the  lumen  was  small  and  even  obliterated.  The 
mucosa,  however,  remained  unchanged.  When  only  one  ovary 
had  been  removed,  there  ivas  no  change  in  the  sexual  development 
of  these  animals,  the  young  ones  evidencing  a  normal  and  con- 
stant development  of  the  genitalia. 

Jentzer  and  Beuttner  examined  the  organs  of  cows  within  one 
year  to  twenty-two  months  after  castration,  and  found  all  the 
layers  of  the  uterus  atrophied  and  substituted  by  connective  tis- 
sue. The  stratum  vasculare  had  greatly  changed ;  the  atrophy  of 
the  mucosa,  while  not  constant,  was  in  most  cases  acute.  They 
castrated  rabbits,  gave  subsequently  hypodermatic  injections  of 
ovarin,  and  yet  the  uterus  atrophied.  The  objections  to  con- 
sidering this  last  procedure  conclusive  are :  1.  That  the  ovarin 
of  cows  was  used.  2.  That  it  was  given  hypodermatically. 
3.  That  there  was  no  sufficient  increase  in  the  amounts  used. 
The  castration  of  other  rabbits  showed  that  the  cylindrical 
epithelium  became  lower,  the  protoplasm  degenerated,  these 
processes  becoming  more  defined  the  longer  after  castration  the 
animals  were  examined.  The  muscularis  was  found  to  be  atro- 
phied ;  the  larger  vessels  were  gone.  Although  glands  were 
present,  the  mucosa  showed  decided  atrophy.  In  dogs  castration 
produced  atrophy  of  the  muscle,  but  only  after  three  or  four 
months ;  the  epithelium  of  the  uterus  was  lower,  the  protoplasma 
cloudy,  the  glands  were  degenerated,  and  the  vessel  walls  thick- 
ened. 

Knauer  transplanted  the  ovaries  of  rabbits  and  dogs  between 
the  fasciae  of  the  abdominal  wall  and  into  the  mesometrium,  be- 
ing careful  to  remove  absolutely  every  bit  of  ovarian  structure. 
In  the  mesentery  he  fastened  the  ovary  with  two  sutures  between 
two  folds  of  peritoneum,  the  ovaries  being  then  nourished 
through  endosmosis  or  through  plasmatic  circulation.  New  ves- 
sels grew  into  the  ovarian  tissue  and  furnished  its  subsequent 
support ;  this  change  began  as  early  as  the  fourth  day.  Examina- 
tion at  various  periods  showed  that  a  small  part  of  each  ovary 
usually  degenerated,  and  new  connective  tissue  appeared  in  place 
of  the  lost  cells.  In  all  cases  in  which  a  complete  degeneration 
of  the  ovaries  was  found,  atrophy  of  the  breasts  and  of  the  geni- 
talia had  occurred.     The  muscle  of  the  uterus  was  atrophied,  the 


THE   PROCESSES   ANTEDATING   UTERINE   GESTATION.  3 

intermuscular  connective  tissue  was  increased,  the  mucous  mem- 
brane was  atrophied — changes  like  those  which  occurred  after 
double  castration.  Retention  of  function  on  the  part  of  the 
transplanted  ovaries  was  always  evidenced  by  the  growth  of  fol- 
licles in  a  normal  manner,  by  the  ripening  of  the  follicles, 
and  by  the  discharge  of  the  ova.  In  all  such  cases  the  nor- 
mal character  of  the  breasts,  of  the  uterus,  and  of  the  geni- 
talia ivas  preserved,  and  in  the  younger  animals  all  these  organs 
underwent  a  natural  development.  In  one  dog  with  well-devel- 
oped breasts,  thirteen  months  after  transplantation  an  opening 
of  the  abdomen  showed  the  right  ovary  to  be  of  normal  size  and 
to  contain  three  follicles.  The  left  ovary  was  small.  Two 
months  later  coitus  took  place,  and  after  two  more  months  two 
well-developed  young  were  born.  Three  years  after  transplanta- 
tion had  been  done,  this  animal  on  examination  showed  externally 
a  normal  condition  of  development  of  the  breasts  and  the  geni- 
talia. The  right  ovary  was  the  size  of  a  pea  and  contained  fol- 
licles ;  the  left  ovary  was  larger  than  on  the  previous  examination. 
The  right  ovary  was  covered  with  germinal  epithelium;  many 
follicles  but  no  primary  follicles  being  present.  A  like  condi- 
tion was  found  in  the  left  ovary.  The  uterus  was  normal  in 
every  way ;  the  mucous  lining  contained  many  glands  and  ciliated 
epithelium.  The  breasts  were  of  normal  character,  with  normal 
secretion  and  glands.  Knauer's  results  proved  that  the  preser- 
vation to  the  organism  of  the  functionating  ovaries  preserves  the 
breasts,  the  genital  organs,  and  the  sexual  instinct,  a  result  pos- 
sible only  through  the  absorption  into  the  circulation  of  ovarian 
secretion,  and  that  the  function  which  the  ovary  exerts  upon  the 
body  stands  in  closest  relation  to  its  ability  to  form  ripe  ova. 
Ovarian  tissue  which  has  ceased  to  develop  ova  has  lost  its  other 
function,  that  is,  secretion.  Therefore  the  numerous  nerves  of 
the  ovary  are  in  all  probability  only  vessel  nerves.  Knauer 
transplanted  in  sixteen  cases  the  ovaries  of  animals  into  each 
other,  obtaining  the  above  good  results  in  only  two  cases,  since  in 
the  others  the  ovaries  degenerated.  This  shows  that  a  certain  re- 
lation exists  between  the  cells  of  one  and  the  same  body.  Al- 
though difficult,  transplantation  of  ovaries  from  one  animal  to 
another  is  possible. 

Morris  removed  the  adnexa  in  a  human  patient  and  sewed  a 
piece  of  one  ovary  into  the  stump  of  the  right  tube.  One  month 
later  the  patient  became  gravid,  aborting  in  the  third  month. 
Into  a  twenty-year-old  girl  with  uterus  infantilis  and  rudimen- 


4  THE   PROCESSES   ANTEDATING    UTERINE    GESTATION. 

tary  adnexa,  with  suppressio  mensium,  he  transplanted  a  piece 
of  the  ovary  of  a  thirty-year-old  patient,  fixing  it  in  the  fundus 
of  the  uterus.  Eight  weeks  later  a  profuse  menstruation,  lasting 
ten  days,  occurred. ;  after  six  weeks  a  normal  one  lasting  five  days ; 
the  third  one  five  days  later.  The  fourth  and  fifth  menstruations 
were  normal,  at  intervals  of  four  weeks. 

Glass  transplanted  an  ovary  of  a  seventeen-year-old  girl  into 
a  twenty-nine-year-old  patient  from  whom  both  ovaries  had  been 
removed  two  years  before.  The  ovary  was  fixed  in  its  normal 
situation  through  an  opening  in  the  sac  of  Douglas,  per  vaginam. 
Sixteen  days  later  occurred  a  bleeding  lasting  two  days ;  six 
months  afterward  a  menstruation  of  three  days ;  eight  months 
after  operation  the  patient  showed  good  color,  was  of  good  ap- 
pearance, with  a  return  to'  former  mental  and  body  conditions, 
after  two  years  of  artificial  climax. 

Dudley  implanted  an  ovary  into  the  fundus  of  the  uterus  after 
removal  of  a  pyosalpinx  duplex,  and  regular  menstruation  con- 
tinued. 

An  examination  of  the  uterus  after  castration  in  women  shows 
an  atrophy  of  the  cervix,  an  immediate  atrophy  of  the  corpus,  a 
sclerosis  of  the  vessels  which  show  a  growth  of  the  intima,  and 
an  endarteritis  obliterans,  especially  in  the  larger  vessels.  Few 
glands  are  present,  and  the  connective  tissue  is  increased. 

Gottschalk  found  an  exceptional  condition  in  one  case,  in  which 
the  muscularis  was  well  preserved,  although  the  mucous  lining 
had  almost  entirely  disappeared. 

Cholmogoroff  found  the  uteri  at  climacterium  to  contain  9 
large  amount  of  connective  tissue,  the  vessels  being  greatly 
sclerosed.  I  have  found  the  same  condition  in  a  high  degree  in 
two  cases  of  my  own. 

Normal  menstruation  is  absolute  evidence  of  the  presence 
of  a  normally  functionating  ovary.  The  absence  of  ovaries,  a 
poor  development  of  these  glands,  an  insufficient  secretion  of 
ovarian  substance,  or  a  diversion  of  ovarian  secretion  to  other 
organs  of  the  body,  always  causes  a  failure  of  uterine  develop- 
ment or  uterine  atrophy.  It  is  possible  that,  with  partial  or  total 
absence  or  atrophy  of  the  uterus  or  other  genital  organs,  normal 
ovaries  may  be  present.  It  is  likewise  possible  for  poorly  de- 
veloped ovaries  to  be  the  result  of  a  failure  of  development  of  the 
body  in  general  or  to  be  simply  a  failure  of  development  of  the 
ovary  itself,  through  embryonal  disturbances. 

Winckel  has  shown  that,  in  the  development  of  the  uterus  and 


THE   PROCESSES   ANTEDATING   UTERINE   GESTATION.  5 

tubes,  the  situation  of  the  Wolffian  Body  close  to  the  ducts  of 
Muller  may  influence,  to  a  very  great  degree,  their  growth  and 
is  a  frequent  cause  of  malformation.  The  early  completion  of 
the  Wolffian  bodies,  their  opening  into  the  sinus  urogenitalis, 
the  growth  of  the  Muller 's  ducts  along  the  Wolffian,  and  their 
crossing  at  that  spot  where  the  union  of  Muller 's  ducts  finds  its 
upper  limit,  are  anatomical  embryological  factors  easily  recognized 
as  causes  of  uterine  maldevelopment  and  hypoplasia.  Further, 
the  origin  of  the  ligamentum  ileo-genitale  rotundum  at  this  up- 
per limit,  its  close  union  with  the  ducts  of  Muller,  the  fact  that 
its  line  of  development  in  a  measure  opposes  the  union  of  the 
ducts,  in  addition  to  tension,  pressure,  and  torsion  exerted  by 
the  neighboring  organs,  such  as  the  Wolffian  bodies,  the  bladder, 
the  ureters,  the  vessels  and  nerves  of  the  uterus  and  rectum,  are 
important  factors  influencing  the  development  of  the  uterus.  In 
addition,  Winckel  recognizes  the  occurrence  of  abnormal  cells  in 
the  septum  between  the  ducts  of  Muller,  and  general  hypoplasia  of 
the  vessel  system,  as  additional  causes  of  maldevelopment.  Aside 
from  secondary  atrophy,  the  result  of  constitutional  diseases,  the 
embryological  cause  here  mentioned,  and  the  forms  associated 
with  general  hypoplasia,  we  recognize  in  the  ovary  and  its  se- 
cretion the  factor  which  governs  the  development  of  the  uterus, 
the  genitalia,  and  the  breasts,  and  the  factor  which  is  concerned 
in  the  preservation  of  these  organs  and  the  regulation  of  men- 
struation. 

Eberlin1  describes  a  patient  with  vaginal  defects,  who,  in  her 
eighteenth  year,  had  vicarious  menstruation  from  the  nose  at 
regular  intervals  for  six  months,  after  which  no  recurrence  was 
noted.  Her  mammae  and  external  genitalia  were  small.  She 
suffered  from  molimina  menstrualia  every  three  weeks,  at  first 
for  periods  of  three  to  four  days.  Eventually  severe  pain  was 
experienced  constantly,  associated  with  sickness  at  the  stomach 
and  vomiting.  Laparatomy  divulged  a  uterus  rudimentarius, 
with  absence  of  the  adnexa  of  the  left  side.  The  right  tube  and 
ovary  were  almost  normal.  The  uterus  was  3.5  centimetres  in 
length,  differing  microscopically  in  nowise  from  the  normal  as  re- 
gards muscle,  but  possessing  no  cavity.  The  ovary  showed  a 
thickening  and  a  hyaline  degeneration  of  the  vessel  walls.  In 
addition  to  the  corpus  luteum,  very  few  follicles  but  no  Graafian 
follicles  were  present.  After  castration  all  the  annoying  symp- 
toms disappeared. 

Fritsch  operated  in  a  like  case  in  which  severe  molimina  men- 
^ineberg,  Am.  Jour,  of  Obstet.,  No.  4,  1898. 


6  THE   PROCESSES    ANTEDATING   UTERINE    GESTATION. 

strualia,  sickness  at  the  stomach,  and  rectal  bleedings  were  the 
indications. 

In  all,  Eberlin  finds  twenty-one  cases  of  this  sort  associated 
with  vagina]  defect  to  have  been  operated  upon.  The  ovary  in 
the  above-cited  case  of  Eberlin,  though  containing  few  follicles, 
nevertheless  secreted  sufficiently  to  cause  the  severe  symptoms. 
Since  no  endometrium  was  present,  and  no  excretion  by  that 
channel  took  place,  the  ovarian  secretion,  through  cumulative 
action,  was  responsible  for  the  severity  of  the  pain.  Whatever 
part  the  uterus  took  in  these  attacks  must  have  deen  the  result  of 
uterine  contraction,  since  congestion  alone  is  not  responsible  for 
so  much  pain,  as  is  evidenced  by  the  absence  of  such  suffering  in 
pure  congestions  of  the  uterus,  associated  with  metritis,  etc. 

B.    CONSTITUTIONAL    CHANGES   DEPENDENT    ON    THE    OVARY. 

Were  we  to  consider  the  relation  between  the  ovary  and  the 
uterus,  and  between  the  genitalia  and  other  organs  to  exist 
through  the  medium  of  the  cerebro-spinal  or  sympathetic  sys- 
tems, why  should  we  find  the  walls  of  the  tubes  thin  and  con- 
taining more  connective  tissue  in  cases  of  poorly  developed 
ovaries  and  at  the  menopause,  when  no  primary  follicles  and  no 
Graafian  follicles  are  present  in  the  ovaries?  The  uterus  then 
shrinks,  the  walls  become  thin  and  flabby,  the  mucous  membrane 
atrophies,  the  connective-tissue  elements  are  more  prominent,  and 
the  ciliated  epithelium  disappears.  Is  it  not  extraordinary  to 
make  the  occurrence  of  these  decided  changes  dependent  upon  a 
cessation  of  ovarian  congestion?  That  these  differences  are  not 
due  to  the  lack  simply  of  reflex  stimulation  on  the  part  of  the 
ovary  is  sufficiently  evidenced  by  the  constitutional  changes  oc- 
curring at  puberty,  at  menstruation,  during  pregnancy,  and  at 
the  menopause.  The  relation  between  the  changes  occurring  at 
puberty  and  at  the  menopause,  before  menstruation  and  after 
menstruation,  during  pregnancy  and  after  pregnancy,  show  a 
decided  resemblance.  Until  shortly  before  each  menstrual 
period,  temperature,  pulse,  muscular  activity,  lung  capacity,  and 
the  excretion  of  urea  increase,  and  reach  their  maximum  two  to 
three  days  before  the  appearance  of  blood.  During  this  period 
we  find  hyperemia,  edema,  increased  activity  of  the  ovary, 
changes  in  all  the  mucous  membranes,  and  increased  function  of 
the  glandular  apparatus.  The  occurrence  of  swelling  of  the 
breasts,  tenderness  of  the  abdomen,  even  pain  and  the  passage 
from  the  vagina  of  increased  mucus,  sometimes  mixed  with  blood, 


THE   PROCESSES    ANTEDATING    UTERINE    GESTATION.  7 

prove  at  the  beginning  of  each  menstrual  period  a  wave  move- 
ment and  an  increased  blood  tension  by  no  possibility  due  to 
reflex  causes.  During  and  after  menstruation  regressive  changes 
are  evident,  and  the  excretion  of  nitrogenous  elements  is  dimin- 
ished. 

During  pregnancy  we  have  an  increased  amount  of  the  watery 
elements  of  the  blood,  an  increased  proportion  of  fibrin,  a  di- 
minished amount  of  albumin,  an  increase  in  the  white  blood  cells, 
a  genuine  increase  in  the  number  of  red  blood  cells  and  in  the 
amount  of  hemoglobin. 

Before  labor  the  temperature  is  highest  in  the  last  three 
months  of  pregnancy,  and  there  is  an  increase  in  the  elements 
of  the  body,  equal  to  one-thirteenth  of  the  body  weight.  This 
increase  is  due  to  serous  infiltration,  and  to  the  increased  ability 
of  the  body  to  form  organized  tissue.  Post  partum,  after  a  tem- 
porarily short  rise,  the  temperature  is  lower,  the  blood  pressure 
sinks,  and  becomes  normal  on  the  ninth  day.  The  loss  in  body 
weight  is  equal  to  one-ninth  of  the  weight  of  the  pregnant  per- 
son. For  labor  and  post  partum  together,  there  is  a  loss  of 
weight  nearly  equal  to  one-fifth  of  the  body  weight  at  full  term. 
After  labor  there  is  a  diminution  of  tissue  change  and  a  diminu- 
tion in  the  amount  of  urine. 

Therefore  as  regards  temperature,  blood  pressure,  body  weight, 
the  amount  of  urine  secreted,  etc.,  there  is  always  a  similar  in- 
crease before  menstruation,  and  a  like  decrease  in  intensity  dur- 
ing and  after  menstruation,  as  during  and  after  parturition,  so 
that  Virchow  has  well  characterized  menstruation  as  being  a 
labor  en  miniature. 

According  to  Loewenthal,  who  believes  that  every  ovum  is  em- 
bedded in  the  mucous  membrane  of  the  uterus,  we  may  say  that 
labor  is  a  menstruation  in  which  a  fully  developed  ovum  is  ex- 
pelled. The  coincidence  of  labor  with  a  menstrual  period  seems 
therefore  natural.  The  resemblance  of  the  mechanical  processes 
concerned  in  menstruation  and  in  labor  is  remarkable,  and  these 
changes  can  be  due  only  to  the  stimulative  effect  of  the  ovarian 
secretion,  acting  not  alone  upon  the  uterus  and  the  genital  organs, 
but  likewise  upon  the  breasts,  upon  the  blood  elements,  and  upon 
blood  tension.  This  secretion  is  a  stimulus  likewise  to  uterine 
contractions,  and  is  the  probable  cause  of  the  contractions  nor- 
mally occurring  during  pregnancy.  The  action  of  this  accumu- 
lated secretion  upon  the  uterus  at  the  end  of  pregnancy  is  prob- 
ably the  cause  of  labor  pains. 


8  THE   PROCESSES   ANTEDATING   UTERINE    GESTATION. 

The  action  of  the  ovarian  secretion  upon  pulse  tension,  and  its 
effect  upon  the  mucous  membranes  of  the  body  generally,  are 
likewise  evidenced  by  the  congestion  of  the  vocal  cords  during 
menstruation,  so  that  during  this  time  the  singing  voice  is  poor. 
The  secretion  of  intestinal  mucus  is  also  greater,  there  is  in- 
creased perspiration,  the  lower  turbinated  bones  are  swollen,  and 
the  eye  suffers  limitations  in  power.  The  best  evidence  of  the 
constitutional  elements  involved  in  the  process  of  menstruation 
is  the  occurrence  of  vicarious  menstruation.  Under  this  designa- 
tion ice  consider  bleedings  occurring  at  regular  intervals  in  a 
patient  suffering  from  amenorrhea.  The  most  frequent  spot  for 
this  bleeding  is  the  nose,  usually  the  lower  turbinated  bones. 

Fleiss  described  a  two-year-old  child  with  well-developed  pubes 
and  breasts  who  had  periodical  bleedings  from  the  nose.  In  a 
second  case,  a  girl  fourteen  years  old,  well  developed,  suffered 
from  regular  bleedings  from  the  nose,  which  stopped,  however, 
Avhen  real  menstruation  began.  In  another  case  the  regular  nose 
bleedings  at  intervals  of  twenty-nine  days  stopped  during  preg- 
nancy, only  to  begin  afterward,  and  after  a  continuation  of  eight 
months  ceased  again  on  the  occurrence  of  a  second  pregnancy. 
Bleedings  of  the  same  kind  have  been  described  as  occurring 
regularly  from  other  mucous  membranes,  the  trachea,  the  lungs, 
and  the  stomach.  In  the  latter  instance  the  bleedings  were  not 
always  associated  with  vomiting,  the  blood  being  usually  found 
in  the  feces.  In  other  cases  there  were  bleedings  into  the  thyroid 
gland.  In  cases  with  poorly-developed  uteri,  these  bleedings  dis- 
appeared only  when  the  uterus  began  to  functionate  properly. 

The  secretion  of  the  ovary  exerts  through  the  medium  of  the 
blood  a  stimulating  effect  upon  the  breasts,  noticeable  before 
menstruation,  during  pregnancy,  and  during  the  period  of  lacta- 
tion . 

(ioltz  cut  through  the  cord  of  a  dog  at  the  level  of  the  first 
lumbar  vertebra,  and  later  saw  the  signs  of  rut  appear.  After 
coitus  one  dead  and  two  living  young  were  born.  The  breasts 
were  well  developed,  and  lactation  and  nursing  followed  the 
normal  course.  Since  these  changes,  the  sexual  tendency  and  the 
process  of  labor  could  not  have  been  excited  through  the  cord,  it 
must  be  that  a  certain  secretion  of  the  ovary,  acting  through  the 
medium  of  the  circulation,  gives  the  stimulus  for  the  exercise  of 
those  functions. 

Ovarian  secretion  exerts  a  most  decided  effect  upon  the  de- 
velopment of  the  uterus  and  the  genitalia,  as  well  as  upon  the 


THE    PROCESSES   ANTEDATING   UTERINE    GESTATION. 

breasts.  It  is  absolutely  necessary  for  the  preservation  of  the 
developed  uterus,  the  other  genitalia,  and  the  breasts.  An  over- 
production of  ovarian  secretion  or  a  disturbance  in  the  function 
of  the  ovary  causes  pathological  changes ;  an  under-production  of 
ovarian  secretion  is  likewise  the  cause  of  pathological  conditions. 
The  production  of  ovarian  secretion  and  its  action  for  a  certain 
period  of  time  are  the  probable  causes  of  the  pains  of  labor. 

C.    MENSTRUATION. 

Menstruation  is  the  periodical  loss  of  blood  from  the  uterus  or 
from  any  mucous  membrane,  occurring  for  the  reason  that  no 
fecundated  ovum  is  present  in  uterus  or  tube,  and  may  be  divided 
into  three  periods :  the  premenstrual,  the  menstrual,  and  the 
postmenstrual.  During  the  premenstrual  period,  the  ten  days 
immediately  preceding  the  appearance  of  blood,  the  following 
changes  take  place : 

The  superficial  capillaries  become  greatly  dilated,  and  serous 
infiltration  of  the  endometrium  takes  place,  which  separates  the 
meshes  of  the  stroma,  accompanied  by  a  gradual  but  decided 
dilatation  of  all  the  blood  vessels  and  lymph  channels.  There 
occur  a  growth  of  round  cells  in  the  interglandular  tissue,  and  an 
entrance  of  leucocytes  into  the  mucous  membrane.  The  glands 
become  larger  and  wider,  being  often  filled  with  secretion. 

This  swelling  of  the  mucous  membrane,  the  dilatation  of  the 
blood  vessels,  the  production  of  round  cells,  and  the  growth  of 
the  superficial  layer  of  the  endometrium  produce  the  so-called 
decidua  menstrualis.  Although  in  the  connective  tissue  large 
cells,  not  to  be  distinguished  from  young  stages  of  decidua  cells, 
are  found,  it  is  to  be  noted  that  typical  decidua  cells  do  not,  as  a 
rule,  develop  at  this  time  in  the  superficial  layer.  The  endo- 
metrium is  at  this  period  from  6  to  7  millimetres  in  thickness. 

The  period  during  which  blood  is  thrown  out  is  the  next,  or 
menstrual  period.  The  superficial  capillaries  are  greatly  dilate'!, 
and  an  exit  of  blood  elements,  not  dependent  on  a  bursting  of  the 
capillaries,  goes  on  for  several  days.  The  bleeding  occurs  partly 
through  diapedesis,  and,  in  strong  bleedings,  through  rhexis. 
There  is  little  or  no  destruction  of  the  mucosa,  only  a  very  slight 
fatty  degeneration  of  the  epithelium  of  the  uppermost  layer,  so 
that  in  the  excreted  blood  relatively  few  epithelial  cells  are 
found. 

After  menstruation,  the  uterus  shows  an  almost  continuous 
covering  of  epithelium,  interrupted  in  spots,  especially  if  patho- 


10  THE   PROCESSES   ANTEDATING   UTERINE   GESTATION. 

logical  processes  be  present.  Most  of  the  ciliated  epithelium 
is  preserved.  The  first  stimulus  to  bleeding  is  due  to  contraction 
of  the  uterus,  which  at  the  height  of  congestion  is  possibly  ac- 
companied by  contractions  of  the  tube.  During  menstruation 
the  uterus  is  larger  and  in  the  first  few  days  following  likewise 
soft  and  flabby.  The  flabbiness  lasts  longer  than  the  bleeding. 
A  spontaneous  dilatation  of  the  cervix  canal  takes  place,  and 
reaches  its  height  on  the  third  or  fourth  day.  This  dilatation 
takes  place  without  regard  to  the  amount  of  blood  discharged, 
whether  the  menstruation  be  painful  or  painless.  The  cervix  is 
hyperemic,  the  glands  showing  an  increased  secretion  of  mucus. 
The  blood  thrown  off  is  mixed  with  the  mucus  of  the  uterus  and 
cervix,  and  later  with  the  acid  secretion  of  the  vagina,  for  this 
reason  coagulating  less  easily  than  other  blood. 

The  secretion  from  the  sebaceous  glands  of  the  external  geni- 
talia is  responsible  for  the  peculiar  odor  present  in  some  cases, 
and  in  nowise  differs  from  that  observed  in  the  axilla.  On  the 
inverted  uterus  the  blood  has  been  observed  to  appear  in  single 
drops  from  the  region  of  the  openings  of  the  glands.  The  endo- 
metrium is  then  covered  with  white  and  bloody  mucus,  the  open- 
ings of  the  glands  being  clearly  seen.  There  is  no  degeneration 
or  destruction  of  the  mucous  membrane.  The  changes  in  the 
tubes,  if  any,  are  slight  (Gusserow). 

The  next,  or  postmenstrual  period  comprises  fourteen  days, 
during  which  the  mucous  membrane  returns  to  a  thickness  of  3 
millimetres.  During  this  time  all  cells  not  capable  of  further 
growth  are  thrown  off,  and  the  epithelium,  only  partially  de- 
nuded, is  regenerated.  The  epithelial  cells  found  singly  or  in 
groups  in  the  lumen  of  the  glands  disappear  by  resorption,  and 
partially  by  phagocytosis.  From  the  sixth  day  after  the  be- 
ginning of  menstruation,  cell  division  is  prominent.  It  is  prob- 
able that  mitosis  takes  place,  even  during  the  exudation  of  blood. 
The  presence  of  mitosis  in  the  leucocytes  is  an  evidence  of  growth 
of  the  interstitial  tissue  during  menstruation. 

Regeneration  concerns  the  stroma,  the  glands,  and  surface 
epithelium,  reaching  its  height  on  the  fourteenth  or  fifteenth  day 
after  the  beginning  of  menstruation.  The  mucous  membrane  be- 
comes pale,  the  glands  and  vessels  have  returned  to  their  normal 
state,  the  lost  epithelium  has  been  restored.  From  the  middle  of 
the  third  week  on  there  is  a  diminution  in  mitosis. 

Menstruation  is  not  a  process  by  which  the  mucous  lining  of 
the  uterus  is  thrown  off,  with  subsequent  regeneration  previous 


THE   PROCESSES   ANTEDATING   UTERINE   GESTATION.  11 

to  the  next  menstruation.  It  is  simply  the  excretion  of  blood 
from  the  decidua  menstrualis  occurring  for  the  simple  and  sole 
reason  that  there  is  in  the  uterus  no  fecundated  ovum. 

Ovarian  secretion  is  the  direct  cause  of  this  periodical  swelling 
of  the  mucosa,  and  it  continues,  if  fecundation  has  taken  place, 
to  exert,  not  alone  a  local,  but  likewise  a  stimulating  influence 
on  the  general  and  sexual  organs.  This  stimulation  occurs  to  a 
heightened  degree  during  pregnancy,  and  on  removal  of  the 
uterus,  since  the  secretion  is  ordinarily  excreted  during  men- 
struation. On  the  occurrence  of  pregnancy,  this  secretion  causes 
a  further  development  of  the  uterus  and  the  decidua,  and  plays 
an  important  part  in  the  process  of  labor;  it  stimulates  the  func- 
tions of  the  breasts,  exerts  a  decided  constitutional  stimulation, 
and  is  the  cause  of  many  of  the  pathological  conditions  occurring 
before  and  during  labor. 

The  generally  accepted  view  as  to  the  relation  between  ovula- 
tion and  menstruation  is  that  of  Pfliiger.  The  increase  of  the 
contents  of  the  Graafian  follicle,  which  results  through  the  se- 
creting activity  of  the  cells  of  the  membrana  granulosa,  is  said 
to  stimulate  the  nerves  running  in  the  stroma  and  ending  in  the 
cells.  The  increasing  tension  reflexly  irritates  the  vasomotor 
centre,  with  resulting  dilatation  and  congestion  of  the  uterine 
vessels.  At  the  height  of  this  congestion  the  follicle  is  supposed 
to  burst,  through  pressure.  As  congestion  and  tension  in  the 
ovary  are  supposedly  the  reflex  causes  of  the  congestion  of  the 
uterus  and  pelvic  organs,  menstrual  bleeding  is  considered  a 
result  of  periodical  ovulation.  This  theory  obtained  support 
through  the  experiments  of  Strassman,  who  showed  that  increased 
tension  in  the  ovaries  of  animals,  produced  by  the  injection  into 
them  of  fluid,  caused  swelling  of  the  mucous  membrane  of  the 
uterus.  In  answer  it  may  be  asked  why  the  same  condition  does 
not  result  in  all  cases  of  ovarian  tumors  and  ovarian  cysts,  which 
may  develop  entirely  beneath  the  albuginea. 

This  theory  of  Pfliiger  and  the  experiments  of  Strassman  have 
been  generally  quoted  to  prove  the  causal  relation  of  ovulation  to 
menstruation.  The  congestion  in  the  ovary,  and  the  swelling  of 
the  Graafian  follicle,  must  then,  through  the  nervous  system, 
stimulate  the  uterus  to  congestion,  with  a  resulting  periodical 
bleeding.  The  cessation  of  menstruation  after  castration  has 
likewise  been  cited  as  proof  of  the  fact  that  without  ovulation 
there  could  be  no  menstruation,  since  the  periodical  hyperemia 
reflexly  caused  by  ovulation  no  longer  takes  place.     By  others  it 


12  THE   PROCESSES   ANTEDATING   UTERINE   GESTATION. 

was  considered  that  the  distension  of  the  ovary,  occurring  periodi- 
cally, exerted  an  action  upon  the  vasomotor  system,  then  causing 
congestion.  The  atrophy  of  the  uterus  after  castration  was  like- 
wise pointed  out  as  a  proof  of  the  resulting  diminished  Mood 
supply,  ordinarily  furnished  by  this  reflex  action  of  the  ovary. 
On  the  other  hand,  it  has  been  frequently  stated  that  the  result 
of  castration  was  due  to  the  tying  off  of  the  arterise  spermatica? 
internas,  and  that  the  resulting  anemia  was  the  cause  of  atrophy 
of  the  uterus,  and  of  the  diminution  in  the  size  of  the  uterine 
myomata. 

Rein  cut  all  the  sympathetic  and  all  the  spinal  nerves  running 
to  the  uterus  in  a  dog,  and  yet  the  animal  bore  young.  Inas- 
much as  the  uterus,  freed  from  the  central  nervous  system,  per- 
formed its  functions  as  before,  he  concluded  that  a  regulating 
nerve  centre  exists  in  the  ovaries.  All  this  was  taken  to  prove 
that  menstruation  was  a  result  of  reflex  action  originating  in  the 
ovaries. 

D.    THE   ACTION    OF    OVARIAN    SECRETION    ON    THE    ENDOMETRIUM. 

The  periodical  swelling  of  the  mucous  membrane  is  due  to  the 
secretion  given  of  by  the  ovary,  and  the  experiment  of  Strass- 
man  proves  that  the  forcing  of  an  additional  amount  of  this 
secretion  into  the  circulation  only  enhances  this  effect.  That 
ovulation  and  menstruation,  or  at  least  the  latter,  occur  with  a 
certain  regularity  is  a  fact  which  we  are  not  able  to  explain  any 
more  than  we  can  say  why  in  malaria  the  plasmodia  are  thrown 
into  the  circulation  at  regular  intervals,  or  why  the  menopause 
usually  occurs  at  a  certain  period.  At  any  rate,  were  men- 
struation the  direct  result  of  periodical  ovulation,  we  should 
still  be  in  need  of  a  satisfactory  explanation  for  the  latter  phe- 
nomenon. No  other  theory  is  satisfactory  than  that  of  secretion. 
Ovulation  and  menstruation  are  evidences  of  the  functional 
capability  of  the  ovary.  Since  ovulation  may  occur  without 
menstruation,  but  the  latter  never  without  the  former,  we  have 
here  an  evidence  that  a  certain  functional  activity  of  the  ovary 
is  necessary  to  stimulate  the  mucous  membrane  to  its  periodical 
changes.  That  after  double  castration  regular  bleedings  may 
occur  for  a  certain  period  is  proof  of  the  independent  role  which 
the  endometrium,  to  a  certain  degree,  plays  in  the  process  of  men- 
struation, for  sufficient  of  the  secretion  of  the  ovaries  may  still 
remain  in  the  circulation  to  produce  the  normal  processes  after 
removal  of  the  ovaries.     The  part  which  the  ovaries  play  in  the 


THE   PROCESSES   ANTEDATING   UTERINE    GESTATION.  13 

development  of  the  body,  the  effect  of  their  presence  upon  the 
breasts  and  the  genital  tract  at  puberty,  before  each  menstrual 
period,  at  the  menopause,  and  after  castration,  are  sufficient  evi- 
dence of  their  secreting  power.  The  experiments  of  Knauer  and 
others  prove  that  it  is  simply  the  presence  of  the  ovaries,  and  the 
preservation  of  their  secretion,  which  are  of  importance  to  the 
body,  and  that  their  action  upon  the  uterus  is  in  nowise  reflex  in 
character,  since  when  removed  and  implanted  elsewhere,  and  in 
this  way  loosened  from  their  connection  with  nerve  plexuses  and 
the  nervous  system,  every  sexual  peculiarity  is  absolutely  pre- 
served. 

Menstruation  is  simply  an  evidence  that  a  fecundated  ovum  is 
not  present  in  the  tube  or  in  the  uterus.  Practically  no  part  of 
the  endometrium  is  thrown  off.  It  seems  as  if  the  blood  thus  lost 
simply  gave  an  exit  to  the  secretion  of  the  ovary,  which,  if  re- 
tained too  long  in  the  body,  produces  in  pregnancy  certain  nor- 
mal changes,  and  in  a  large  number  of  cases  abnormal  processes. 
In  pregnancy  the  ovarian  secretion  stimulates  the  uterus  to  en- 
largement and  growth,  it  stimulates  the  formation  of  blood,  pro- 
duces tension  and  congestion  in  the  vascular  system,  and  stimu- 
lates the  function  of  the  breasts.  After  labor,  lactation  is  stimu- 
lated by  this  secretion,  so  that  little  or  no  effect  is  exerted  upon 
the  uterus ;  therefore  it  rarely  undergoes  the  periodical  stimula- 
tion and  has  a  tendency  to  atrophy.  The  changes  occurring  in 
the  decidua  menstrualis  and  the  decidua  graviditatis  are  cer- 
tainly evidences  of  the  action  of  a  secreted  substance.  The 
method  in  which  the  ovum  is  embedded  in  the  decidua,  and  the 
processes  occurring  in  its  immediate  vicinity,  as  well  as  the  fact 
that  in  extrauterine  gravidity  a  decidua  graviditatis  is  formed 
in  the  uterus,  with  decided  enlargement  of  this  organ,  are  like- 
wise proofs  of  this  fact. 

E.    THE    RELATION    OF    OVULATION    AND    MENSTRUATION. 

As  a  matter  of  fact,  ovulation  and  menstruation  are  related 
only  in  that  both  are  the  result  of  the  secreting  function  of  the 
ovary,  and  are  in  nowise  connected  as  regards  cause  and  effect. 
The  ovum  is  the  external  secretion,  the  internal  secretion  enter- 
ing the  blood  through  the  lymph  channels.  The  ripening  and 
expulsion  of  an  ovum  may  occur  at  any  time.  It  is,  however,  a 
fact  that  menstruation  occurs  only  after  the  ovary  is  capable  of 
producing  ripe  ova,  and  whether  the  egg  be  expelled,  or  occa- 
sionally  degenerate   in   the   follicle,   is  immaterial.     The   inde- 


14  THE   PROCESSES   ANTEDATING   UTERINE    GESTATION. 

pendenee  of  ovulation  and  menstruation  is  evidenced  by  the  fact 
that  the  former  takes  place  before  menstruation  has  appeared, 
and  likewise  after  the  menopause,  as  is  proven  by  cases,  by  no 
means  rare,  of  pregnancy  in  girls  who  have  not  yet  menstruated, 
as  well  as  by  the  occurrence  of  pregnancy  at  variable  periods 
after  the  amenorrhea  of  the  climacterium.  In  children  the  pri- 
mary follicles  develop  fully  before  puberty,  and  the  same  devel- 
opment occurs  even  in  the  fetus  and  in  the  newly  born.  Those 
ova  and  follicles  go  through  the  same  stages  of  development  an. I 
ripening  as  in  the  case  of  adults.  That  they  are  not  capable  of 
fecundation  is  shown  by  the  fact  that  the  ova  are  only  one-half  as 
large  as  in  adults.  In  those  cases,  however,  of  young  children 
with  well-developed  breasts  and  genitalia,  when  menstruation  be- 
gins there  is  an  unusually  strong  development  of  the  body,  and 
the  ova,  as  well  as  the  follicles,  differ  in  no  way  from  those  found 
in  menstruating  adults. 

Leopold  found  that  in  forty-two  pairs  of  ovaries,  thirty  pairs 
showed  a  corpus  luteum  belonging  to  the  last  menstruation.  In 
thirteen  pairs  no  follicles  were  found  which,  on  account  of  their 
size  or  the  swelling  of  the  follicle,  justified  a  belief  that  a  burst- 
ing of  any  follicle  would  have  occurred  at  the  next  menstrual 
period.  In  twelve  cases  no  corpus  luteum  was  found  belonging 
to  the  last  menstruation.  One  case  showed  a  follicle  which  had 
burst  between  menstrual  epochs. 

Arnold  found  that  in  fifty-four  cases,  only  thirty-nine  showed 
the  presence  of  fresh  corpora  lutea  after  the  last  menstrual 
period. 

Williams  found  this  to  be  the  case  in  twelve  cases  out  of  six- 
teen. Therefore,  ovulation,  although  in  the  majority  of  cases 
occurring  at  or  near  the  menstrual  period,  is  not  the  cause  of 
the  same. 

Leopold  has  shown  experimentally  that  in  the  inter-menstrual 
period  follicles  ready  to  burst  are  present,  and  that  through  cer- 
tain causes,  such  as  coitus,  the  exit  of  an  ovulum  may  result  at 
any  time.  That  ovulation  occurs  during  pregnancy  is  proved  in 
the  case  mentioned  by  Kroenig,  in  which  conception  occurred  as 
a  result  of  coitus  four  days  post  partum.  The  relatively  fre- 
quent occurrence  of  pregnancy  during  the  temporary  amenor- 
rhea of  lactation  is  a  proof  of  ovulation  during  this  time. 

Consentino  finds  that  during  pregnancy  and  lactation  ovula- 
tion continues.  Although  the  ovum  of  a  menstrual  period  may  be 
fecundated  immediately  thereafter,  the  ovum  usually  fecundated 


THE   PROCESSES   ANTEDATING   UTERINE    GESTATION.  15 

is  the  one  given  off  between  four  and  eight  days  before  men- 
struation, the  egg  thus  belonging  to  the  period,  so  to  say,  first 
omitted.  The  ovum  retains  its  vitality  for  an  average  period  of 
twelve  days,  and  yet  out  of  a  collection  of  two  hundred  and 
fourteen  pregnant  cases,  in  sixty- five  coitus  had  taken  place  after 
the  twelfth  day  following  menstruation.  Therefore,  in  these 
pregnancies  at  least,  the  ovum  must  have  belonged  to  what  may 
be  called  the  next  awaited  menstrual  period.  Even  if  the  ex- 
pulsion of  the  ovum  occur  only  a  few  days  before  that  time,  its 
fecundation  is  not  difficult  to  explain,  nor  are  the  cases  puzzling 
in  which  one  coitus  directly  after  menstruation  produces  preg- 
nancy, as  the  spermatozoa  retain  their  vitality  for  a  long  time, 
and  have  been  preserved,  in  proper  temperature,  for  a  period  of 
eight  days.  Duhrssen  has  found  spermatozoa  in  the  tube  three 
and  one-half  iveeks  after  the  last  coitus. 

It  is  therefore  evident  that  ovulation,  as  a  rule,  occurs  from 
four  to  eight  days  before  menstruation,  but  it  may  occur  at  other 
periods,  as  ripe  ova,  practically  speaking,  may  be  present  at  al- 
most any  time. 

F.    OVULATION. 

The  other  of  the  functions  of  the  normal  ovary  is  the  production 
and  expulsion  of  ova  capable  of  being  fecundated.  It  is  probable 
that  after  birth  no  new  ova  are  formed  from  the  germinal  epithe- 
lium. At  and  after  puberty  we  judge  the  vitality  of  the  ovary 
by  its  ability  to  bring  these  ova  to  a  stage  which  may  be  called 
ripe.  For  the  expulsion  of  an  ovum  from  the  Graafian  follicle,  a 
gradual  increase  in  size  of  the  follicles  takes  place,  depending 
partly  on  an  increase  in  the  amount  of  liquor  folliculi.  The  cells 
of  the  follicle  epithelium  undergo  fatty  degeneration,  and  the 
internal  layer,  the  tunica  interna,  shows  an  increase  in  the  size 
of  the  cells,  and  a  decided  development  of  the  blood  vessels.  The 
protoplasm  enlarges  greatly,  begins  to  take  on  a  yellow  color, 
and  these  cells,  now  lutein  cells,  are  arranged  in  several  layers, 
forming  an  irregular  surface.  As  a  result  of  the  fatty  degenera- 
tion of  the  follicle  epithelium,  the  ovum  is  freed  from  the  cumu- 
lus oophorus.  The  most  prominent  point  of  the  follicle  is  poor 
in  blood  supply,  and  furnishes  the  so-called  stigma  folliculi.  It 
is  here  that  the  opening  takes  place  which  serves  as  an  outlet 
for  the  ovum.  This  opening  is  probably  the  result  of  the  re- 
action or  chemical  effect  produced  by  the  ripe  ovum,  since  in  the 
newly  born,  and  in  children,  follicles  of  the  same  size  and  even 


16  THE   PROCESSES   ANTEDATING   UTERINE   GESTATION. 

larger  ones  exist  without  bursting — the  so-called  atresic  follicles. 
The  facts  that  large  follicle  cysts  occur  in  the  ovary  without 
opening,  and  also  that  in  women  in  whom  the  unopened  follicles 
degenerate,  disturbances  of  menstruation  occur — so-called  missed 
ovulation — speak  for  a  chemical  reaction  as  probably  one  of  the 
functions  of  the  ripe  ovum.  That  the  orgasmus  venereus  does 
play  a  part  in  hastening  the  expulsion  of  the  ovum  is  not  to  be 
questioned.  In  most  cases  the  opened  follicle  is  then  filled  with 
blood  which  likewise  empties  into  the  peritoneal  cavity,  and  the 
so-called  corpus  luteum  spurium  results.  If  pregnancy  takes 
place,  this  body  develops  decidedly,  forming  the  corpus  luteum 
verum  (Nagel). 

After  ovulation,  the  ovum  is  thrown  out  into  the  abdominal 
cavity,  and  then,  influenced  by  the  wave  movement  of  the  ciliated 
epithelium  of  the  tubes,  the  fimbria?  of  the  ampulla,  and  the 
fimbria?  ovarica?,  finds  its  way  into  the  uterus.  It  is  not  neces- 
sary that  the  tube  should  grasp  or  surround  the  ovary,  since  it 
would  embrace,  even  under  favorable  circumstances,  only  part 
of  the  ovary.  This  wave  movement  of  the  ciliated  epithelium 
causes  a  current  in  the  peritoneal  plasma,  which  directs  the  ovum 
into  one  or  the  other  of  the  tubes. 

Lode  injected,  with  a  needle  pointed  toward  the  diaphragm, 
the  eggs  of  ascarides  into  the  abdominal  cavity  of  rabbits,  in  the 
region  of  the  umbilicus.  After  ten  hours,  without  the  excitement 
of  coitus,  he  found  these  eggs  in  the  tube.  An  interesting  proof 
of  the  existence  of  this  current  is  given  by  Knauer,  who  removed 
the  ovaries  of  dogs,  and  sewed  them  into  the  mesentery.  In  one 
case,  on  opening  the  abdomen  he  saw  in  one  of  the  ovaries  three 
ripe  Graafian  follicles.  Shortly  after,  coitus  took  place,  and  in 
due  time  two  young  were  born.  A  further  proof  is  found  in  the 
experiments  of  Leopold,  who  showed  that  an  ovum  given  off  by 
one  ovary  may  enter  the  tube  of  the  other  side.  The  cases  are 
not  rare  in  which  the  tube  of  one  side  was  closed  or  absent,  and 
although  the  corpus  luteum  verum  was  found  in  the  ovary  of  the 
same  side,  yet  the  ovum  was  found  in  the  uterus.  The  same  is 
true  of  those  cases  in  which  the  corpus  luteum  verum  is  on  one 
side,  and  the  ovum  develops  in  the  other  tube,  or  in  the  horn  of  a 
uterus  unicornis  of  the  opposite  side.  Therefore  it  is  certain 
that,  normally,  a  wave  current  exists  on  either  side  of  the  uterus, 
and  that  the  ovum  is  attracted  by  the  stronger  current,  usually 
that  of  the  side  from  which  it  came,  possibly,  however,  by  the 
current  of  the  other  side. 


THE   PROCESSES   ANTEDATING    UTERINE    GESTATION.  17 

It  is  therefore  evident  that  an  ovum,  by  natural  means,  may  at 
any  time  enter  the  tubes,  and  that  no  congestion  of  the  tube,  no 
erection  of  the  tube,  and  no  reflex  spasmodic  grasping  of  the 
ovary  by  the  tube  are  necessary. 

Lode  has  shown  that  an  ovum  finds  its  way  through  the  tube 
into  the  uterus  in  thirty  hours. 


OHAPTEE   II. 

THE  EMBEDDING  OF  THE  OVUM  IN  THE  GUINEA-PIG. 

A.    UTERUS   OF    THE   GUINEA-PIG. 

The  uterus  of  the  guinea-pig  is  six  centimetres  long  and  con- 
sists of  two  muscular  layers,  an  external  longitudinal  one  closely 
connected  with  the  peritoneum,  and  an  internal  circular  one. 
Sometimes,  within  the  latter,  are  found  isolated  bands  of  longi- 
tudinal fibres. 

Between  the  two  muscular  layers  is  a  broad  zone  of  loose  con- 


Qland 
Uterine  lumen 


Fig.   1. — Half-schematic  section  of  the  uterine  horn  of  a  guinea-pig.     (v.   Spee.) 


nective  tissue,  and  in  this  are  found  the  continuations  of  the  ves- 
sels which  enter  through  the  longitudinal  layers  at  the  mesome- 
tral  area.  All  the  larger  vessels  are  in  the  circular  layer.  Their 
walls  lose  the  muscularis  and  their  continuations  then  enter  the 
specific  parenchyma  of  the  uterus,  where  they  appear  as  capil- 
laries or  simple  endothelial  channels. 

The  uterine  lumen  is  lined  with  a  single  uninterrupted  layer 
of  cylindrical  epithelial  cells ;  no  cilia  are  clearly  seen.  This 
epithelial  layer  descends  into  the  connective  tissue  at  numerous 
places,  into  glands  lined  with  a  low  epithelium.     The  peripheral 


EMBEDDING   OF   THE   OVUM    IN    THE    GUINEA-PIG.  19 

ends  of  the  glands  are  twisted  and  extend  up  to  the  circular  layer. 
An  active  increase  of  epithelial  cells  through  mitosis  takes  place 
only  in  the  end  areas  of  the  glands,  so  that  here  the  regenerative 
stations  for  the  uterine  epithelium  are  to  be  sought.  In  other 
areas  of  the  uterine  lining  the  epithelial  cells  have  lost  the  power 
to  produce  new  cells.  This  is  the  case  in  animals  in  ivhom  the 
epithelium  plays  no  part  in  the  formation  of  the  placenta. 

The  connective  tissue  consists  of  two  zones  separated  by  a 
transition  zone.  (1)  A  peripheral  zone  surrounding  the  twisted 
gland  ends  and  consisting  of  spindle  or  branching  cells  with  in- 
tervening spaces,  resembling  a  loose  reticular  connective  tissue. 
(2)  A  central  compact  zone  situated  between  the  straight  ex- 
cretory ducts  of  the  glands.  In  the  implantation  of  the  ovum 
only  this  area  is  invaded.     Extremely  numerous  mitoses,  and  the 

1 

Vt.    epith. 


Pig.  2. — Cells  of  the  compact  zone  with  the  epithelial  lining  of  the  uterine 
lumen  of  the  guinea-pig.    (v.  Spee.) 

varying  appearance  and  thickness  of  their  tissue,  are  proofs  of 
active  changes  and  an  increased  tissue  change.  Since  at  points 
not  important  the  strongest  cell  increase  may  be  found,  the  con- 
clusion is  justified  that  the  life  of  the  connective-tissue  cells  of 
the  uterus  is  short.  There  are  no  spindle-shaped  or  branching 
cells  here  as  are  found  in  the  peripheral  zone. 

The  cells  of  the  central  zone  (Fig.  2)  lie  like  the  cells  of  stratified 
epithelium.  They  are  polygonal,  close  together,  generally  sep- 
arated by  sharp  contours,  which  are  probably  intercellular  spaces. 
The  most  firmly  uniting  basis  is  furnished  by  the  capillary  net- 
work, for  a  real  connecting  factor  among  the  elements  of  the  con- 
nective tissue,  especially  of  the  compacta,  is  not  present.  The 
normal  relation  is  preserved  by  the  firmly  united  epithelium  and 
the  circular  muscular  layer,  between  which  lie  the  two  layers  of 
connective  tissue. 


20  EMBEDDING   OP    THE   OVUM    IN    THE   GUINEA-PIG. 

B.    THE    EMBEDDING   OP    THE    GUINEA-PIG 'S   OVUM. 

In  1883  Spee  stated  that  on  the  sixth  day  post  coitus  the  ovum 
of  the  guinea-pig  is  an  oval  germinal  vesicle  one-tenth  of  a  mil- 
limetre in  diameter,  surrounded  by  a  zona  pellucida  and  lying 
free  in  the  uterine  cavity  (Fig.  3).  The  cell  wall  of  the  vesicle, 
the  germinal  layer,  consists,  in  the  region  of  the  ovum's  equator, 
of  a  single  layer  of  very  flat  cells.  At  the  two  poles  the  wall  seems 
thicker.  At  one  pole  the  cell  wall  of  the  vesicle  is  stratified  and 
forms  a  prominence  into  the  cavity  of  the  vesicle,  the  Germinal 
Prominence  of  Hensen  or  the  Placental  Pole  (P.  P.).  At  the 
other  pole  (the  Opposite  Pole  of  Spee)  the  germinal  layer  con- 
sists of  a  single  layer  of  cubical  cells,  constituting  the  Implanta- 
tion Pole  (LP.).  It  forms  after  implantation  that  summit  of  the 
ovum  into  which  the  embryonal  sphere  enters  and  in  which  the 
embryo  develops. 


Zona 


Pig.  3. — Ovum  of  guinea-pig  free  in  the  uterine  cavity.  Ovum  with  zona. 
Note. — The  lettering  of  Pig.  3  is  reversed,      (v.  Spee.) 

The  zona  is  preserved  up  to  the  beginning  of  the  seventh  day 
post  coitus  and  can  be  readily  seen  on  the  free  germinal  vesicle. 
The  cubical  cells  of  the  Implantation  Pole  send  prolongations  of 
their  cell  bodies  through  the  zona  and  can  enter  into  direct  rela- 
tion with  the  epithelial  lining  of  the  uterus  before  the  zona  is 
lost  finally  to  the  ovum,  and  may  so  furnish  the  first  connection 
ivliich  leads  to  implantation.  These  prolongations  have  been 
seen  only  in  the  region  of  the  Implantation  Pole.  The  short 
period,  during  which  the  prolongations  of  the  Implantation  Pole 
hold  the  ovum  fixed  to  the  uterine  epithelium,  however,  has  not 
been  observed. 

When  the  ovum  is  first  attached  to  the  uterine  epithelium  the 
zona  is  present  (Fig.  3a),  but  disappears  in  a  very  short  time,  for 
it  is  not  seen  in  embedding  ova.  Probably  the  Implantation  Pole 
prolongations  perforate  it  and  cause  its  disappearance  at  these 


EMBEDDING   OF   THE   OVUM   IN    THE    GUINEA-PIG. 


21 


points.  The  rest  is  probably  rubbed  off.  In  irrigating  a  uterus 
for  ova,  Spee  once  found  the  cell  body  of  an  ovum  and  an  empty 
zona  with  a  hole  large  enough  to  have  permitted  the  former  to 
slip  out.  Acids  dissolve  the  zona,  and,  as  these  were  often  used 
in  fixing  the  specimens,  the  fact  that  no  zona  was  found  in  the 
youngest  ova  which  had  entered  the  uterine  wall  does  not  prove 
that  the  ova  were  embedded  after  removal  of  the  zona.  The  ova 
during  implantation,  however,  are  so  closely  surrounded  by 
uterine  tissue  that  between  them  there  is  no  room  for  a  zona,  and 
so  in  all  probability  the  ovum  does  not  take  the  zona  with  it  into 
the  uterine  wall. 

The  Embedding  or  Implantation  of  an  Ovum  includes  the 
group  of  processes  which  result  in  the  ovum  entering  from  the 


Zona. 


Ut.  epith. 


Zona 


Ut.  ep. 


Gland 


vV/3  o  'Ox 


%i 


Fig.  3a. — Ovum  of  guinea-pig  in  its  first  adhesion  to  the  uterine  epithelium. 
Ovum  still  possesses  its  zona.      (v.   Spee.) 

uterine  cavity  into  the  connective  tissue  of  the  uterine  wall. 
The  processes  antedate  the  formation  of  the  placenta  and  are  dis- 
tinct from  the  processes  of  placental  formation,  hut  the  first  evi- 
dences of  the  latter  follow  immediately  upon  implantation.  In 
the  guinea-pig,  ova  are  never  implanted  at  a  point  at  which  or 
in  whose  neighborhood  signs  of  circulatory  disturbances  (exces- 
sive collection  of  tissue  exudation  in  the  interstices  of  the  sub- 
epithelial connective  tissue,  or  a  grouping  of  red  blood  cells  in 
these  interstices),  or  evidences  of  a  throwing  off  of  tissue  into  the 
uterine  lumen,  are  noted.  Only  such  areas  are  selected  as  are 
normal  and  whose  tension,  dependent  on  tissue  sap,  is  even, 
which  fact  coincides  with  the  observation  that  the  uterine  lumen 
at  the  selected  point  always  shows  a  surprisingly  smooth  epithe- 
lial lining  without  folds. 


22 


EMBEDDING   OP    THE   OVUM    IN    THE    GUINEA-PIG. 


The  ovum  is  almost  always  embedded  on  the  anti-mesometral 
side,  corresponding  to  the  fundus  uteri  in  the  human  being,  and 
beings  about  6  days,  8  to  12  hours  post  coitus,  seldom  later  at  the 
end  of  the  seventh  day.  The  time  left  for  embedding  is  4  to  8 
hours.  Its  beginning  is  known  with  a  possible  variation  of  about 
6  hours.  The  ovum  does  not  increase  in  size  before  its  embed- 
ding, and  measures  with  the  zona  only  0.1  millimetre,  without  the 
zona  0.08  millimetre,  while  the  uterus  is  6  centimetres  long.  As 
often  only  one  or  two  ova  are  present  and  as  their  location  is  not 
macroscopically  evident,  only  series  sections  divulge  the  various 
points.  If  the  ovum  is  already  through  the  uterine  epithelium, 
it  is  seen  with  difficulty  because  of  its  small  size.  One  may 
readily  imagine  the  labor  involved  in  obtaining  the  present  un- 


IttllSl- 


Fig.  4. — b,  capillary  ;  v,  vacuole ;  c,  cavity  in  ovum.     Ovum  of  guinea-pig  par 
tially  embedded,  showing  disappearance  of  the  uterine  epithelium,      (v.  Spee.) 


broken  series  illustrative  of  the  various  stages,  a  work  on  which 
Spee  has  been  engaged  for  the  last  ten  years. 

•  The  cells  of  that  pole  which  leads  all  other  parts  in  its  entrance 
into  the  uterus  (I.  P.)  send  prolongations  through  the  zona 
shortly  before  the  implantation  period,  and  render  contact  and 
exchange  with  the  uterine  epithelial  cells  possible,  even  before 
the  zona  is  gone.  These  prolongations  cause  the  first  adhesion  of 
the  ovum  to  the  uterine  epithelium  (Fig.  3a). 

The  uterus  plays  a  passive  role  in  implantation  of  the  ovum. 
The  ovum  enters  the  uterine  wall  and  a  correspondingly  large 
space  of  uterine  tissue  disappears. 

The  uterine  epithelium  shows  no  sign  of  growth. 

The  uterine  epithelium  of  just  that  area  in  contact  with  the 
ovum  disappears   (Fig.  4). 


EMBEDDING   OP    THE   OVUM    IN    THE   GUINEA-PIG. 


23 


In  Fig.  4  the  ovum  is  6  days  and  10  hours  post  coitus,  and 
evidences  no  zona.  A  thin  cell  layer  (a)  surrounds  for  a  dis- 
tance the  cavity  (e)  of  the  ovum  on  one  side,  but  is  not  distinct 
on  the  other  side.  The  solid  portion  of  the  ovum  consists  of  large 
round  cells  which  are  not  surrounded  by  a  cell  covering.  Only 
at  a  is  there  a  flat  cell  which  stands  in  continuity  with  the  cell 
membrane  enclosing  the  cavity  of  the  ovum  (e).  The  mem- 
branous portion  of  the  ovum  contains  two  small  vacuoles   (v). 


A 


Antimcsometral 


Nuclei  in  the 
symplasma 


Nuclei  in  the 
symplasma 


Pig.  5. — Further  stage  in  embedding  of  ovum,  showing  changes  wrought  in  the 
connective  tissue  compacta.  (v.  Spee.)  x,  two  cells  of  the  ovum  which  are  em- 
bedded on  the  opposite  side. 


The  central  cavity  is  lined  with  a  non-celled  coagulation  sub- 
stance, which  has  divided  the  cavity  into  two  parts,  probably  a 
postmortem  change.  The  external  surface  of  the  solid  area  is 
not  covered  by  a  specially  differentiated  layer  of  flat  cells.  The 
solid  group  of  cells  represents  the  placental  pole.  The  cavity 
e  represents  the  germinal  cavity.  The  part  of  the  ovum  near  the 
connective  tissue,  at  the  Implantation  Pole,  is  the  cell  wall  of 
the  cavity,  the  germinal  membrane.     The  space  between  the  cells, 


24 


EMBEDDING    OF    THE   OVUM    IN    THE    GUINEA-PIG. 


and  the  thin  layer  near  the  connective  tissue,  later  becomes  filled 
with  cells,  forming  a  solid  ovum. 

Decided  changes  occur  in  the  connective  tissue  which  makes 
room  for  the  ovum.  These  changes  for  a  long  time  are  such  as 
may  be  considered  a  necrosis  and  a  paralysis  of  the  life  processes 
of  the  connective-tissue  cells  (Fig.  5). 

Fig.  5  shows  a  double  embedding  at  two  points  vis-a-vis.  The 
ovum  evidences  no  cavity.  The  ovum  is  already  deep  in  the  wall 
and  the  uterine  epithelium  is  interrupted  in  the  circumference  of 
the  ovum.     The  surrounding  connective-tissue  cells  have  changed 

Nuclei       Sumplasma       Boundary  of  conn,  tissue 


Symplasma 


Kg 
Conn,  tissue 
border 


Capillary 


Uterine  epithelium 

Fig.  6. — Further  stage  of  embedding  of  guinea-pig's  ovum,  showing  the  con- 
nective tissue  compacta  about  the  ovum  destroyed  by  the  bio-chemical  influence 
of  the  ovum.     (v.  Spee.)     c,  centre  of  ovum  ;  G,  embryonal  sphere. 


in  that  a  half -moon  arranged  row  of  connective-tissue  cells  of  a 
stronger  stain  has  been  formed.  The  cells  of  the  ovum  are 
much  larger  than  the  connective-tissue  cells.  To  the  left  at  x 
two  cells  of  the  ovum  are  united  to  the  uterine  epithelium,  and 
two  others,  not  distinctly  seen,  have  perforated  the  uterine 
epithelium.  The  single  layer  about  the  ovum  at  I.  P.  is  the  ger- 
minal layer  plus  the  implantation  pole.  The  cell  group  at  the 
placental  pole  has  grown  into,  and  filled  out,  the  germinal  vesicle, 
but  the  ovum  is  not  enlarged.  Therefore  the  ovum  now  evi- 
dences no  cavity.     The  sharp  contour  at  o  bounds  the  connective 


EMBEDDING   OP    THE   OVUM    IN    THE    GUINEA-PIG. 


25 


tissue  sharply  and  is  independent  of  the  cell  body  of  the  ovum. 
That  the  cells  of  the  ovum  dissolve  the  epithelium  with  which 
they  come  in  contact,  is  seen  in  its  early  stages  at  x,  where  four 
cells  are  present.  The  connective-tissue  cells  about  the  ovum  are 
large  and  polygonal  with  sharp  contours  and  of  epithelioid  form. 
This  form  also  is  found  in  certain  areas  away  from  the  ovum, 
and  is  there  dependent  on  other  influences  than  the  ovum.  This 
change  in  the  cells  extends,  and  this  area  is  called  the  Implanta- 
tion Area.  During  this  peripheral  extension  the  cells  nearest  to 
the  ovum  show  other  changes  in  the  nuclei.  They  stain  darker. 
This  is  due  to  a  process  of  dissolution,  and  as  a  matter  of  fact 


Boundary  of   connective    tissue 


Capillary 


Cap. 


Pig.  7. — A  stage  of  embedding  one-half  hour  later  than  Pig.  6  (v.  Spee). 
more  highly  magnified.  G,  embryonal  sphere.  The  ovum  is  surrounded  by  a 
symplasmatic  zone. 


the  nuclei  nearest  to  the  ovum  are  already  smaller  and  mitosis  ha3 
ceased  in  the  immediate  circumference  of  the  ovum. 

The  connective-tissue  cells  are  fluidified  by  a  form  of  digestion. 
The  disappearance  of  mitosis  for  a  considerable  distance  about 
the  ovum,  the  dissolving  of  the  connective-tissue  cells  immediately 
about  the  ovum,  while  at  a  distance  normal  cell  division  takes 
place,  show  that  the  destruction  of  uterine  tissue  is  due  to  a  bio- 
chemical process  dependent  on  the  ovum  (Fig.  6). 

Fig.  6  is  still  further  embedded,  and  in  four-fifths  of  its  cir- 
cumference is  a  single  layer  of  cells,  the  germinal  layer.  This 
is  connected  at  the  placental  pole  with  a  solid  mass,  the  germinal 


26 


EMBEDDING    OF    THE    OVUM    IN    THE    GUINEA-PIG. 


prominence,  which  fills  the  space  surrounded  by  the  germinal 
layer.    The  Implantation  Pole  is  situated  on  either  side  of  8. 

In  Fig.  7  the  ovum  is  situated  half  in  the  epithelium  and  half 
in  the  subepithelial  connective  tissue.  The  ovum  is  sharply 
bounded  from  the  connective  tissue.  It  is  surrounded  by  a  sym- 
rplasmatic  zone  in  which  a  histolytic  process  causes  the  contours 
and  nuclei  of  the  connective-tissue  cells  to  disappear,  as  if  the 
ovum  were  a  poison.  The  ovum  consists  of  a  covering  layer  and 
a  contained  mass   (G)   of  large  cells  containing  fat.     A  small 

Symplasma        Capillary 

o  A CrX 


Capillary 
Nuclei 

umplasma 


iff©0 


Capillary 


'ocP 


00  Oi 


Fig.   8. — Almost  embedded  ovum  surrounded  by  fluid  resulting  from  fluidified 
connective  tissue  cells,     (v.  Spee. ) 


space  separates  the  ovum,  in  part,  from  the  connective  tissue 
(C.  t). 

The  ova  6,  7,  and  8,  though  differing  only  about  half  an  hour 
in  age,  produce  great  changes  in  the  connective  tissue.  Ovum 
No.  6  is  about  three-fourths  embedded.  Ova  7  and  8  were  found 
in  the  same  uterus.  Only  in  8  is  a  growth  of  the  ovum,  as  com- 
pared with  5,  evident.  Important  are  the  connective-tissue 
changes,  first  in  the  cells  of  the  Implantation  Area,  and,  second, 
in  the  boundary  line  which  faces  the  ovum.     Ovum  No.  8  is  al- 


EMBEDDING   OF    THE   OVUM    IN    THE    GUINEA-PIG. 


27 


most  embedded  and  several  of  its  cells  are  on  a  line  with  the 
uterine  epithelium.  A  comparison  of  ova  6  and  8  evidences  two 
differences,  which  show  the  two  varying  functions  in  two  differ- 
ent parts  of  the  ovum,  (1)  the  part  consisting  of  the  external 
layer,  a  derivative  of  the  germinal  layer,  and  the  Implantation 
Pole;  (2)  the  cell  mass  at  the  Placental  Pole.  In  the  circumfer- 
ence of  the  Implantation  Pole  the  connective-tissue  cells  beneath 
the  epithelium  disappear  or  degenerate.  The  cells  at  the  Placental 
Pole  do  not  destroy  the  uterine  tissue,  therefore  the  hole  in  the 


Symplasma  ^~!{®:fjy~r 
Vacuoles 


a  s. 
Assimilation 
border  of  the     -^  *.v» 
implantation     m*®* 
area 


Fig.  9. — Ovum  entirely  under  the  uterine  epithelium,  a.s.,  assimilation  bor- 
der of  the  implantation  area  ;  y,  embryonal  sphere  ;  H,  fluid  space  about  ovum, 
(v.  Spee.) 


uterine  epithelium  at  the  Placental  Pole  of  ovum  8  is  not  en- 
larged. 

In  the  Implantation  Area  the  connective-tissue  cells  and  the 
nuclei  become  large.  The  chromatin  of  the  nuclei  becomes 
grouped  on  the  inner  surface  of  the  nuclear  membrane,  but  the 
nuclear  centre  is  pale.  Peripheral  to  the  implantation  zone 
numerous  mitoses  are  observed  and  are  also  found  in  the  vessel 
endothelia.  A  dense  tissue  results  and  the  cell  interstices  disap- 
pear, as  may  be  seen  in  Pig.  9.  This  very  peripheral  area  has  no 
meaning  with  regard  to  implantation  or  to  placental  formation. 

In  Pig.  5  the  cells  nearest  the  ovum  stain  darker  and  are 
smaller.     In  Fig.  6  a  contour  divides  the  connective  tissue  near 


28 


EMBEDDING   OP    THE   OVUM   IN    THE   GUINEA-PIG. 


the  ovum  from  the  ovum,  but  instead  of  numerous  cells  and 
nuclei  we  see  a  fibred,  granular  mass,  a  group  of  closely  gathered 
nuclei  without  cell  contours.  In  Fig.  7  some  nuclei  are  still  well 
stained,  but  lie  in  a  fibred,  granular  mass  in  which  no  cell  con- 
tours are  evident.  A  symplasma  has  been  formed  through  the 
dissolution  of  the  connective-tissue  cells  of  the  implantation  zone 
which  is  sharply  marked  off  from  the  ovum. 

The  ovum  is  then  almost  surrounded  by  fluid  residting  from 
these  changed  cells  (Figs.  8,  9,  10). 

In  Fig.  8  the  symplasma  is  separated  from  the  ovum  by  the 


Capillar!) 


Capillaries 


Symplasma 
mass 


Ovum 


Fig.  10. — A  further  stage,  showing  demarkation  of  the  symplasma,  thus  limit- 
ing the  assimilation  of  future  areas,  n,  free  nuclei  in  the  symplasma.  (v 
Spee.) 


space  H,  which  is  wider  than  in  Fig.  7.  In  the  periphery  are 
smaller,  darker  cells  ready  to  join  the  symplasma.  Here,  then, 
is  the  assimilation  boundary  of  the  symplasma,  The  space  H  is 
filled  with  a  fluid  into  which  the  edge  of  the  symplasma  passes 
over  gradually.  This  constitutes  the  dissolution  boundary  of 
the  symplasma.  The  contents  of  the  space  H  are  a  thin  emulsion 
which  is  under  pressure,  causing  the  circular  contour  of  the 
symplasma  in  Fig.  9. 


EMBEDDING    OP    THE    OVUM    IN    THE    GUINEA-PIG. 


29 


The  fluidifying  of  the  symplasma  occurs  not  only  at  its  edge 
but  in  its  substance,  and  becomes  porous  and  filled  with  vacuoles 
which  contain  fluid  (Figs.  8  and  9).  In  Fig.  9  the  vacuoles  are 
present  in  large  number.  At  the  assimilation  boundary  at  a.  s. 
are  seen  darker,  smaller  cells.  At  /  (Fig.  10)  is  seen  a  sharp 
demarkation  of  the  symplasma  of  the  implantation  zone  which 
limits  the  assimilation  of  future  areas.  The  nuclei  of  the  last 
assimilated  cells  lie  at  this  area  of  separation,  in  short  simple  rows. 
They  furnish  almost -the  same  picture  as  the  nuclei  in  the  syn- 
cytial or  plasmodial  formations  in  the  placenta  of  other  animals. 
The  symplasma  degenerates  and  the  original  boundary  of  H 
formed  by  it  disappears. 

Sympl. 


„>- 


Sympl. 


Nuclei 


Sympl. 


Nuclei 

Fig.  11. — Ovum  entirely  embedded  in  connective  tissue  compacta,  showing 
spaces  (H)  in  the  fibred  tissue  about  the  ovum.  The  fibred  tissue  about  the 
ovum  contains  numerous  granules.  This  is  a  middle  stage  between  the  normal 
compacta  and  the  final  fluid  symplasma.      (v.  Spee.) 


Along  the  epithelial  lining  the  subepithelial  cells  become 
smaller,  and  darker  areas  of  separation  appear  between  them 
and  the  epithelium  leading  up  to  complete  loosening  of  the  latter. 
The  subepithelial  cells,  fluidifying,  form  lacunae  in  the  sub- 
epithelial connective  tissue  (Fig.  12). 

This  fluid,  through  diffusion  or  possible  absorption  by  the 
ovum,  makes  place  for  the  ovum,  which  only  now  begins  to  grow 
quickly.  Later,  at  the  boundary  between  necrotic  and  healthy 
tissue,  a  real  granulation  tissue  is  formed  as  an  active  reaction  to 
the  entering  ovum  (Fig.  12). 

In  the  transition  zone  appear  granular  cells,  which  increase 


30 


EMBEDDING   OF    THE   OVUM   IN    THE    GUINEA-PIG. 


from  Fig.  9  on,  and  eventually  forming  a  characteristic  zone  in 
the  far  periphery,  in  which  the  cells  also  seem  clouded.  Soon 
a  separation  of  the  implantation  area  from  the  connective  tissue 
occurs  at  the  transition  zone  through  great  growth  of  cells  in  the 
peripheral  areas,  and  through  a  stoppage  of  growth  and  degener- 
ation in  the  implantation  area.  The  capillaries  pass  through 
this  boundary  and  on  their  walls  are  grouped  connective-tissue 
cells.     They  are  numerous  at  the  point  of  separation,  so  that  the 

b.c. 


b.c. 


Ovum 


space  bet.  epith.    and  conn,  tissue 
Fig.   12. — g,   embryonal  sphere  ;   n,  free  nuclei   of  the  syrnplasina  ;    b.c,   capil- 
laries.    The  ovum  has  grown.     Ovum  has  a  cavity,  except  at  implantation  pole, 
where  the  embryonal  sphere  is  in  contact  with  the  external  layer  of  the  ovum, 
(v.   Spee.)      Completely  embedded,  growing  ovum. 

wall  looks  like  a  granulating  wound  surface  of  endothelial  chan- 
nels. The  space  about  the  ovum  is  gradually  rilled  with  granu- 
lation tissue  in  the  next  twelve  hours.  Seven  days  post  coitus 
the  ovum  has  groAvn  considerably  (Fig.  12).  The  Placental  Pole 
evidences  a  papulation  of  the  germinal  layer  which  gives  this  end 
a  half-cylindrical  groove,  due  to  two  lateral  folds.  The  ovum 
now  evidences  a  cavity,  except  at  the  Implantation  Pole,  where 
the  embryonal  sphere  is  in  close  contact  with  the  external  mem- 
brane of  the  ovum. 


EMBEDDING   OF    THE    OVUM    IN    THE    GUINEA-PIG.  31 

Seven  days  thirteen  and  one-half  hours  post  coitus  the  ovum 
has  grown  large  (Fig.  13).  The  space  between  the  embryonal 
sphere  and  the  Placental  Pole  has  grown  decidedly,  so  that  the 
ovum  is  a  long,  cylindrical  vesicle,  with  its  Placental  Pole  in  con- 
tact with  the  uterine  epithelium. 

The  investigations  of  Spee  show  that  the  ovum,  of  the  guinea- 
pig,  not  grown  since  its  fecundation,  destroys  like  an  injurious 
parasite  the  uterine  epithelium  and  the  subepithelial  connective 
tissue  to  make  place  for  itself  in  the  uterine  wall  in  which  it  is 
embedded,  and  that  only  after  this  does  it  enter  into  a  symbiotic 
connection  with  the  uterus,  which  connection  finds  its  expression 
in  the  formation  of  a  placenta.  The  same  occurs  with  the  human 
ovum. 


CHAPTER  III. 


THE    EMBEDDING    OF    THE    HUMAN    OVUM. 

A.    THE   UTERUS. 

For  many  years  it  had  been  taught  that  the  human  ovum  in 
the  uterus  developed  on  the  mucosa  (decidua  serotina)  and  was 
enveloped  by  mucosa  growing  up  about  it  (decidua  reflexa). 


..VJ-iYv.,. ;         ',", 

'£!'*& I   — mv''  '    V'  Embryonal  sphere 


till* 

Vy<S^ — l£&''.f      ^ -"*•   epithelium 


Uterine  lumen 


Fig.  13. — Cavity  in  ovum  between  embryonal  sphere  and  placental  pole  has 
grown  greatly,  g,  embryonal  sphere.  (v.  Spee.)  Rapidly  growing,  embedded 
guinea-pig  ovum. 

In  the  examination  of  young  human  ova  Spee  was  never  able 
to  find  uterine  epithelium  lining  the  bed  in  which  the  ovum 
rested,  and  he  doubted  the  theory  that  the  uterine  mucosa  and  its 
epithelium  grew  up  and  surrounded  the  ovum.  Hensen  had 
made  the  observation  that  the  ovum  of  the  guinea-pig,  on  the 
seventh  day  post  coitus,  was  no  longer  to  be  found  free  within 
the  uterus,  and  that  on  the  eighth  day  it  was  located  in  the  uter- 
ine wall  underneath  the  epithelial  lining  (Fig.  13).  Selenka,  on 
the  other  hand,  supported  the  view  that  the  ovum  of  the  guinea- 
pig  entered  into  a  uterine  gland  whose  epithelium  was  later  de- 
stroyed. 


EMBEDDING    OP    THE    HUMAN    OVUM.  ■>■> 

The  relation  between  ovum  and  uterus  varies  in  different  ani- 
mals. There  are  forms  in  which  the  uterine  epithelium  is  pre- 
served at  the  point  at  which  the  ovum  is  attached.  In  all  those 
cases  in  which  the  ovum  grows  before  its  attachment,  it  remains 
during  its  entire  development  within  the  lumen  of  the  uterus  or 
in  a  portion  of  the  same.  The  closer  relation  between  ovum  and 
uterine  wall  develops  later.  In  the  case  of  ova  which  do  not 
grow  at  that  stage,  the  epithelium  disappears.  The  smaller  the 
ovum,  and  the  smaller  the  area  of  uterine  wall  necessary  for  its 
attachment,  the  more  intensely  is  the  uterine  tissue  affected  by 
the  ovum,  so  that  the  area  affected  at  this  point  becomes  rapidly 
very  large  in  proportion  to  the  size  of  the  ovum,  and  naturally 
the  development  of  close  connection  between  ovum  and  uterus 
occurs  earlier  than  in  the  first  class.  Early  attachment  and  small 
ovum  are  therefore  favorable  to  the  nourishment  of  the  latter. 
A  most  favorable  feature  for  the  ovum  is  the  form  in  which  the 
fecundated  germinal  vesicle,  without  any  increase  in  growth,  is 
completely  embedded  in  the  subepithelial  connective  tissue  of  the 
uterus.  Such  is  the  case  with  ova  of  the  rat,  mouse,  guinea-pig, 
and  human  being. 

Decidua  Menstrualis. — In  the  menstrual  decidua  the  super- 
ficial capillaries  become  greatly  dilated,  and  serous  infiltration 
of  the  endometrium  takes  place,  which  separates  the  meshes  of 
the  stroma,  accompanied  by  a  gradual  but  decided  dilatation  of 
all  the  blood  vessels  and  lymph  channels.  There  occur  a  growth 
of  round  cells  in  the  inter  glandular  tissue  and  an  entrance  of 
leucocytes  into  the  mucous  membrane.  The  glands  become 
larger  and  wider,  being  often  filled  with  secretion  (Fig.  14). 

This  swelling  of  the  mucous  membrane,  the  dilatation  of  the 
blood  vessels,  the  production  of  round  cells,  and  the  growth  of 
the  superficial  layer  of  the  endometrium  produce  the  so-called 
decidua  menstrualis.  Although  in  the  connective  tissue  large 
cells,  not  to  be  distinguished  from  young  stages  of  decidua  cells, 
are  found,  it  is  to  be  noted  that  typical  decidua  cells  do  not,  as 
a  rule,  develop  at  this  time  in  the  superficial  layer.  These 
round  cells  are  the  beginnings  of  the  decidua  cells.  The  endo- 
metrium is  at  this  period  from  6  to  7  millimetres  in  thickness. 

Decidua  Graviditatis  in  the  First  Week. — On  the  occur- 
rence of  pregnancy,  as  will  be  noted  below,  the  superficial  por- 
tion of  the  mucosa  is  later  composed  mainly  of  cells  and  is  called 
the  compacta.  The  deeper  layer  is  composed  mainly  of  glands 
and  is  called  spongiosa.  In  the  first  week,  however,  as  may  be 
3 


34 


EMBEDDING    OF    THE    HUMAN    OVUM. 


seen  from  the  description  of  Peters,  there  is  a  decided  division 
into  compacts,  and  spongiosa  only  near  the  ovum.  There  is  at 
this  time  no  real  decidua  elsewhere  and  no  difference  exists 
between  the  connective-tissue  cells  of  the  superficial  and  deep 
layers.     The   tissue   between   the    glands,    however,    is    thicker 


Fig.  14. — Menstrual  decidua.  a,  section  through  vessels  surrounded  by  groups 
of  round  cells  ;  h.  interglandular  tissue  consisting  of  normal  cells  with  scattered 
round  cells  ;  d,  section  of  a  gland  somewhat  dilated — its  epithelia  are  somewhat 
smaller  than  normal.      (Abel.) 


toward  the  surface.  We  find  spindle-shaped  connective-tissue 
cells  mainly.  The  spaces  between  the  cells  are  filled  with  a  pale 
homogeneous  plasma,  and  the  tissue  looks  like  reticular  embry- 
onal connective  tissue.  The  nuclei  in  the  more  superficial  cells 
are  somewhat  larger,  and  numerous  small  round  cells  are  pres- 


EMBEDDING    OF    THE    IJUMAN    OVUM.. 


35 


ent  which  represent  the  early  stages  of  decidua  cells.  The 
epithelium  of  the  superficial  glands  and  of  the  uterine  surface 
is  somewhat  flattened.  An  hypertrophy  of  the  glands,  espe- 
cially in  the  deeper  layers,  is  present,  and  in  transverse  section 
they  are  lined  with  papillary  projections  on  which  are  long, 


Fig.  14a. — Decidua  in  intrauterine  pregnancy  (abortion)  at  the  second  month 
{curetting),  a,  section  of  a  gland  with  flattened  epithelia  :  b,  interstitial  tissue 
consisting  of  the  so-called  decidua  cells,  between  which  at  certain  points  irregu- 
larly-scattered round  cells  are  seen  ;  c,  section  of  a  vessel — in  the  wall  are  endo- 
thelia.      (Abel.) 


high,  cylindrical  cells,  often  looking  like  beaker  cells.  Numer- 
ous epithelia  are  found  free  in  the  glands.  These  glandular 
changes  are  marked  mainly  near  the  ovum. 

Decidua  Graviditatis. — These  typical  changes  occur,  chrono- 
logically, at  a  later  period  in  the  entire  uterus.     Since,  however, 


36  EMBEDDING    OF    THE    HUMAN    OVUM. 

they  are  marked  in  the  first  two  weeks  immediately  about  the 
ovum,  they  are  mentioned  now.  It  is  especially  necessary  to 
consider  the  base  in  which  the  ovum  develops,  as  it  is  difficult 
at  all  times,  even  as  early  as  the  first  week,  to  distinguish  in 
many  areas  between  fetal  and  maternal  cells.  The  mucosa  of 
the  pregnant  uterus,  at  its  thickest,  increases  to  ten  times  its 
original  depth  by  the  growth  of  all  its  elements.  At  the  end  of 
the  first  month  it  is  one  centimetre  thick.  Its  surface  is  uneven, 
deep  grooves  dividing  into  irregular  fields.  These  changes  are 
greatest  at  the  fundus.  In  the  region  of  the  internal  os  the 
changes  are  less  marked,  the  lining  of  the  cervix,  except  for  a 
high  degree  of  hyperemia,  having  no  part  in  these  changes.  The 
increase  in  the  volume  of  the  decidua  depends  greatly  upon  the 
growth  of  round  cells  in  the  endometrium  and  upon  their  change 
into  decidua  cells.     The  round  cells  of  the  connective  tissue,  sit- 


'^-'4*-  • '*"  <£&♦ 

"..»'?»*-*  •■  «      r£  T,» 

i  '•'  '^  B 

Fig.  14b. — A  gland  in  the  decidua  graviditatis,  showing  the  erroneously  named 
"syncytial  change"  of  the  lining  epithelium.  Taken  from  the  curetted  mucosa 
of  a  uterus  two  weeks  gravid. 

uated  in  a  meshwork  of  spindle-  and  star-shaped  cells  forming 
the  stroma,  enlarge.  The  protoplasm  increases  greatly  in 
amount  and  the  nucleus  becomes  larger.  The  cells  are  closely 
grouped,  pale  and  epithelial  in  appearance  (Fig.  14a).  They 
are,  like  the  connective-tissue  cells  of  the  normal  uterus,  infil- 
trated by  capillaries  and  larger  vessels  whose  endothelium  bor- 
ders immediately  on  the  individual  cells.  The  nuclei  are  round 
and  long,  8  to  10  pi  long  and  10  to  12  ju  wide.  They  stain  lightly 
because  their  chromatin  network  is  very  fine.  There  are  nucleoli. 
Mitosis  is  rarely  observed,  but  two  nuclei  may  be  present.  They 
generally  retain  their  spindle-shaped  form  or  are  round  poly- 
gonal. There  is  often  a  fine  space  between  the  individual  cells, 
filled  with  a  homogeneous  intercellular  substance.  These  cells 
appear  at  first  in  the  upper  layer,  and  so  prominently  that  this 


EMBEDDING    OF    THE    HUMAN    OVUM. 


:u 


layer  of  the  gravid  decichia  is  called  the  compacta.  Later,  as  a 
result  of  pressure,  the  cells  resemble  squamous  epithelium. 

The  external  layer  near  the  muscle  contains  so  many  gland 
lumina  that  the  interglandular  tissue  is  in  the  background.  This 
interglandular  tissue  disappears  more  and  more,  so  that  finally 
a  tissue  honeycombed  by  glands  results.  This  layer,  in  contrast 
to  the  superficial,  is  known  as  the  spongiosa.  The  compacta  is 
thrown  off  with  the  ovum;  the  spongiosa  remains  to  regenerate 
the  glands. 

The  gland  cells  lose  their  cylindrical  form  and  become  cubical 
and  spherical.  The  protoplasm  grows  and  the  nuclei  are  there- 
fore further  apart.  Into  the  gland  extend  prominences  cov- 
ered with  groups  of  epithelium  (Fig.  145).  Sometimes  the  eel] 
boundaries  become  indistinct,  giving  the  so-called  "syncytial 
change, ' '  which  has  nothing  to  do,  however,  with  real  syncytium. 


Ovum 


Glands 


Fig.   15. — Schematic  representation  of  the  earliest  stage  in  the  embedding  of 
the  human  ovum.      (Peters.) 

The  epithelium  of  the  surface  is  subjected  to  pressure  and  is 
flattened,  becoming  later  thin  as  endothelium. 

B.    THE   EMBEDDING    OF    THE    HUMAN    OVUM. 

Spee  and  von  Herff  have  shown  that  in  the  guinea-pig  the 
ovum  forms  an  opening  through  the  epithelial  lining  of  the 
uterus,  and  that,  after  having  passed  entirely  through  the 
mucous  membrane,  it  develops  further  in  the  region  of  the 
subepithelial  connective  tissue.  The  opening  thus  formed  is 
closed  by  lymph  exudation,  and  there  results  about  the  ovum 
a  so-called  lymph  space,  showing  that  an  exchange  between 
the  ovum  and  the  surrounding  tissue  exerts  upon  the  latter 
a  certain  reaction.  That  the  same  process  of  centrifugal  descent 
of  the  ovum  into  its  bed  occurs  in  the  human  being  is  to  be 
expected,  for  the  following  reasons:  1.  By  analogy  with  the 
above  process.     2.  In  human  beings  there  is  no  epithelium,  nor 


38 


EMBEDDING   OF    THE   HUMAN    OVUM. 


are  there  any  gland  openings  on  the  surface  of  the  so-called 
reflexa,  facing  the  ovum.  3.  The  youngest  human  ova  found 
in  the  uterus  show  no  prominence  into  the  uterine  cavity,  which 
would  be  the  case  if  they  developed  upon  the  decidua  vera  and 
were  surrounded  by  a  decidua  reflexa. 

Ovum  in  the  Earliest  Stages. — Peters  examined  a  growing- 
ovum  supposedly  three  clays  old.  The  uterus  was  slightly  en- 
larged and  soft.  The  decidua  at  the  fundus  and  on  the  posterior 
wall  was  8  millimetres  thick ;  on  the  anterior,  5  millimetres.  The 
lining  of  the  cervix  was  hyperemia.  On  the  posterior  wall  was 
a  slight  prominence,  which  proved  to  be  the  ovum,  whose  largest 
diameter  was  found  to  be  1.6  millimetres.  The  ovum  was  em- 
bedded in  the  compact  part  of  the  decidua,  which  portion,  as 

Granulation 
and  fibrin  plug 


Decidna 


0 


(y     I  frv — ~— : i  """' 


{^ 


Fig.  16. — Schematic  representation  of  a  centrifugally  embedded  human  ovum. 
(Peters.)      The  summit  of  the  capsularis  is  closed  by  a  fibrin  plug. 

before  stated,  showed  only  a  slight  prominence.  The  summit 
of  the  ovum  was  not  covered  by  a  capsule,  but  showed  a  spot  of 
blood  granulation. 

Only  in  the  immediate  circumference  of  the  ovum  was  there 
a  clear  division  into  compacta  and  spongiosa.  The  nearer  to 
the  ovum,  the  more  frequently  were  free  red  and  white  blood 
cells  found  between  the  cells  of  the  stroma  and  in  the  plasma. 
Nowhere  was  there  an  evidence  of  fatty  changes  in  the  super- 
ficial layers.  The  mucosa  was  everywhere  extremely  vascular. 
The  venous  channels  showed,  superficially,  often  only  a  simple 
canal  of  thin  endothelium,  without  adventitia.  The  arteries  pre- 
served their  adventitia  up  to  the  covering  epithelium.  The 
nearer  to  the  ovum,  the  greater  was  the  vascularization.  In  this 
case  fecundation  took  place  shortly  before  the  expected  men- 


i<:mi;ki>i>in<;  of  tjiu  jiuman  ovum. 


39 


strual  period.  The  fact  that  this  ovum  had  made  its  way  into 
the  decidua,  wherein  it  was  firmly  embedded,  proves,  analogous 
to  the  observation  of  Spee,  that  an  ovum  can  develop  only  on  a 
spot  free  of  epithelium,  and  that,  through  reaction  upon  the  sur- 
rounding tissue,  an  ovum  sinks  into  the  decidua,  and  that  this 
reaction  causes  a  dilatation  of  the  surrounding  lymph  spaces, 
with  a  resulting  localized  edema  (Fig.  20). 

In  the  edges  of  the  groove  in  which  the  ovum  was  embedded, 
and  also  deeper  clown,  a  more  decided  hemorrhagic  edema  took 
place  and  minute  blood  extravasations  forced  their  way  up  to 
the  epithelium  and  lifted  it  off.  The  resulting  coagulation,  con- 
taining likewise  the  remains  of  these  cells,  serves  to  close  the 
opening  and  to  cover  the  ovum  (Fig.  16). 

Capsularis. — In  place  of  the  old  view  of  a  reflexa  growing  up 
and  above  the  ovum  supposedly  situated  on  the  epithelium 
lining  the  uterus,  a  centrifugal  descent  of  the  ovum  must  be 
taken  for  granted.  In  v.  Spee's  young  ovum  the  capsularis  had 
not  yet  united  at  the  summit.  In  Leopold's  case  (ovum  seven  to 
eight  days)  union  had  already  occurred.  In  Peters'  case  the 
summit  was  closed  by  fibrin.  Leopold  and  almost  all  investi- 
gators find  the  structure  at  this  point  atypical.  The  same 
changes  are  found  as  Sanger  remarked  in  the  organization  of 
hematocele  capsules,  i.e.,  fibrin,  connective  tissue,  and  capillaries. 
Keibel,  Kollman,  and  Reichert  say  that  at  the  summit  of  the 
capsule  union  results  in  the  formation  of  what  may  be  called 
a  cicatrix,  to  which  is  given  the  name  cicatrix  of  Reichert. 

As  proof  of  the  ready  and  early  connection  between  maternal 
blood  and  fetal  tissues,  it  may  be  mentioned  that  the  tissue  which 
separates  the  capillaries  from  the  uterine  epithelium  becomes 
extremely  thin  in  the  decidua  menstrualis.  The  capillaries 
which  run  a  twisted  course  between  the  glands  of  the  spongy 
layer  extend  up  to  the  epithelium  under  the  mucosa.  In  the 
compacta  or  superficial  layer  they  often  possess  only  an  endo- 
thelial wall.  When  the  ovum  sinks  into  the  decidua  the  decidua 
basalis  presents  in  addition  a  huge  dilatation  of  the  capillaries. 
The  zone  which  surrounds  the  ovum  is  formed  by  the  compacta. 
As  the  ovum  descends,  gradually  more  compacta  surrounds  it, 
forming  the  so-called  enveloping  zone. 

The  Enveloping  Zone  is  the  layer  of  the  compacta  immediately 
about  the  ovum.  It  furnishes  the  blood  supply  to  the  growing 
blastocyst.  Through  its  edematous  infiltration  it  renders  the 
centrifugal  descent  of  the  ovum  easy. 


CHAPTER  IV. 

THE  EARLY  DEVELOPMENT  OF  THE  HUMAN 

OVUM. 

The  early  cell  division  taking  place  in  an  ovum  is  a  more  or 
less  even  increase,  which  later  gives  way  to  a  development  along 
specific  lines  in  certain  and  well-distinguished  areas,  so  that 
larger  or  smaller  cell  complexes  pass  through  varying  phases 
leading  ultimately  to  the  production  of  embryonal  and  extra- 
embryonal  structures.  Preliminary  to  this  stage  the  cells'  of  the 
ovum,  which  lie  loosely  together  in  the  earliest  period  of  cell 
division,  become  more  closely  united,  so  that  an  epithelium  is 
formed.     The  epithelial  membranes  resulting  from  this  early  cell 


Fig.  17.  Fig.  17a. 

Fig.  17. — Scheme  of  ovum  at  stage  of  simple  chorion  ectoderm  and  entoderm. 
Fig.  17a. — A,  amnion.     Scheme  of  ovum  with  formation  of  amnion  from  the 
ectoderm. 

division  are  called  germinal  layers  (Fig.  17).  It  is  in  them  that 
the  various  specific  areas  of  development  subsequently  appear. 
On  the  two  germinal  layers  (ectoderm  and  entoderm)  lining  the 
germinal  vesicle  or  ovum  and  on  the  subsequent  complexes  of 
these  layers,  two  surfaces  are  to  be  distinguished:  (1)  An  inner 
surface  or  base  facing  the  cavity  of  the  ovum,  and  (2)  an  ex- 
ternal or  free  surface.  The  various  cells  of  a  germinal  layer 
may  increase  or  advance  in  either  direction.  If  the  cells  ad- 
vance from  the  basal  side  this  constitutes  an  invagination;  if 
from  the  free  surface,  an  outgrowth  or  papulation. 

The  germinal  vesicle  increases  in  size  through  an  increase  of 
fluid  in  its  centre,  and  is  composed  of  two  original  boundary 


EARLY  DEVELOPMENT  OF  THE  HUMAN  OVUM.  41 

layers  lying  together:  an  outer,  the  chorion  ectoderm,  and  an 
inner,  lining  the  cavity,  the  entoderm.  This  combination  is  called 
the  germinal  vesicle  and  probably  represents  the  stage  im- 
mediately after  embedding.  At  a  certain  point  is  an  oval 
area,  the  area  embryonalis,  in  which  appears  an  additional 
very  small  cavity,  the  amniotic  cavity,  in  the  wall  of  which  the 
embryo  first  appears.  The  exact  mode  of  this  production  cannot 
be  positively  stated,  but  it  follows  one  or  two  closely  allied  forms. 
It  may  be  formed  through  an  invagination  of  the  ectoderm  (Fig. 
17a),  the  folds  in  the  area  of  invagination  lying  close  together 
and  uniting  quickly,  thus  leaving  within  the  ectoderm  a  small 
enclosed  cavity.  The  very  smallest  amniotic  cavities  (flying-dog, 
guinea-pig)  are  formed  by  a  solid  group  of  cells  passing  out  from 
the  ectoderm  and  finally  becoming  separated  from  it.     In  the 


Germinal  plate 


Fig.  175.  Flg.  17c. 

Fig.  176. — Ovum  with  ectodermal  amnion  separated  from  the  chorion  ecto- 
derm.    A,  amnion. 

Fig.  17c. — Ovum  with  ectoderm,  entoderm,  amnion,  germinal  plate,  but  no 
mesoderm.      (Schematic.) 

centre  of  this  solid  group  the  subsequent  amniotic  cavity  de- 
velops (Fig.  175). 

The  early  amniotic  cavity  of  the  human  ovum  is  extremely 
small.  In  no  animals  where  an  amniotic  cavity  is  formed 
through  the  production  of  reflected  and  approaching  germinal 
folds  does  such  a  small  amniotic  cavity  result.  Therefore  the 
amniotic  cavity  of  the  human  ovum  follows  either  of  the  two 
aforementioned  processes.  By  either  of  these  two  methods,  then, 
an  amniotic  cavity  passes  out  from  the  ectoderm  and  pushes  the 
entoderm  toward  the  central  space  of  the  germinal  vesicle.  (It 
is  possible  that  the  amnion  develops  in  the  embryonal  sphere  of 
Fig.  13.  We  know  little  about  the  origin  of  the  entodermal 
space,  and  it  is  described  as  the  lining  of  the  germinal  vesicle, 
although  it  is  possible  that  it  develops  in  a  manner  resembling 


42 


EARLY   DEVELOPMENT    OP    THE   HUMAN    OVUM. 


the  amniotic  cavity.)  In  the  human  ovum,  in  all  probability, 
the  early  stage  consists  of  small  ectodermal  amniotic  cavity 
sunk  into  a  depression  in  the  closed  yolk  vesicle  lined  with 
entoderm,  these  being  surrounded  by  the  single  layered  ecto- 
blast  vesicle,  the  later  chorionic  ectoderm  (Fig.  17c).  At  this 
stage  no  mesoderm  is  present. 

On  a  portion  of  the  ectodermal  lining  of  the  amniotic  cavity 
appears  an  area,  the  primitive  streak.  The  cells  about  it  become 
differentiated  into  the  ectodermal  germinal  plate  (the  future 
embryo).  In  the  primitive  streak  is  a  furrow — the  primitive 
furrow — which  lies,  therefore,  in  the  middle  of  the  later  germinal 
plate.     By  a  growth  of  cells  of  the  germinal  plate  on  either  side 


Germinal  plate 


Germinal  plate 


Pig.  18. 


Fig.  18a. 


Pig.   18. — Ovum  showing  the  beginning  of  a  mesodermal  growth  at  the  caudal 
end  of  the  germinal  plate.      (Schematic.) 

Pig.  18a. — Ovum  with  completed  growth  of  mesoderm.      (Schematic.) 


and  over  the  primitive  furrow  (primitive  medullary  plates)  a 
canal  results — the  medullary  canal  (Fig.  30a). 

There  begins,  with  the  appearance  of  the  amniotic  cavity  and 
the  differentiation  of  a  portion  of  its  lining  into  the  ectodermal 
germinal  plate,  the  development  of  mesoderm  at  the  caudal  end 
of  the  latter  (Fig.  18).  This  growth  of  mesoderm  begins  close 
to  the  inner  surface  of  the  chorion  ectoderm  and  forms  (1)  a 
thick  mesodermal  mass,  the  caudal  knot  of  the  primitive  streak, 
extending  about  the  caudal  side  of  the  amnion  up  to  the  chorion 
(Fig.  18)  ;  (2)  thin  mesodermal  layers  which  grow  between  the 
chorion  ectoderm  and  the  ectodermal  amniotic  cavity,  and  the 
entodermal  yolk  vesicle. 


EARLY   DEVELOPMENT    OP    THE    HUMAN    OVUM. 


43 


In  the  schematic  drawings  the  entodermal  yolk  vesicle  has  been 
drawn  large  to  make  the  relations  clear.  Whatever  its  size  may 
have  been  at  the  beginning,  and  whether  it  originates  as  a  very 
small  vesicle  in  an  embryonal  nodule  or  not,  it  is  certain  that  on 
growth  of  the  mesoderm  the  amniotic  and  yolk  cavities  are 
found  in  the  embryonal  area  of  the  ovum  and  take  up  a  rela- 
tively small  portion  of  it. 


Beginning  mesodermal  slit 


Entoderm     Entoderm 


Fig.  19. — A  part  of  the  periphery  of  the  ovum  of  Peters,  showing  actual  con- 
ditions pictured  schematically  in  Fig.  18a.  Yolk  sac  is  very  small  compared 
with  Fig.  18a,,  and  naturally  the  amount  of  mesoderm  below  the  germinal  plate 
and  the  yolk  sac  is  much  larger  than  in  Fig.  18a.     Fig.  19  is  the  E.F.  of  Fig.  20. 


The  ectoderm  of  the  ovum  develops  hugely,  forming  the 
chorionic  ectodermal  cover  or  trophoolast. 

This  stage  is  well  represented  in  the  embryonal  formation  of 
Peters  (Fig.  19).  The  ovum  is  surrounded  by  chorion  ectoblast 
formation.  Cells  are  more  plentiful  in  the  mesoderm  near  the 
chorion,  but  the  mesoderm  is  thick  only  in  the  region  of  the 
embryonal  formation.  The  internal  part  of  the  oval  cavity  is 
poor  in  cells,  between  which  is  a  weakly  staining,  fibred,  granular 


44  EARLY   DEVELOPMENT   OP    THE   HUMAN    OVUM. 

mass.  The  embryonal  formation  consists  of  two  small  epithelial 
cavities,  the  ectodermal  amniotic  and  the  entoderm  yolk  ves- 
icle surrounded  by  mesoderm  and  embedded  in  a  thickening 
of  the  mesoblast  near  the  chorion.  The  amniotic  cavity  is  en- 
tirely closed.  Its  wall  is  differentiated  into  the  very  thin  amni- 
otic membrane  and  into  the  germinal  plate,  composed  of  high 
cylindrical  cells.  Between  these  and  the  entoderm  cells  of  the 
yolk,  the  future  umbilical  vesicle,  is  a  layer  of  mesoderm  cells, 
which  are  separated  from  the  ectoblast  area  of  the  amnion  by  a 
membrana  prima  which  always  develops  at  the  border  between 
ectoderm  and  mesoderm. 


EARLY    DEVELOPMENT    OP    THE    HUMAN    OVUM. 


45 


DIVISION   INTO   EMBRYONAL   AND   EXTRA-EMBRYONAL   AREAS. 

Through  the  appearance  of  a  slit  in  the  entire  circumference 
of  the  mesoderm  beginning  at  the  caudal  end  of  the  germinal 
plate,  but  not  dividing  the  dense  mass  of  mesoderm  at  the  caudal 
end,  the  amnion  with  its  germinal  plate  and  the  future  umbilical 
vesicle  are  separated  from  the  chorion  ectoderm  up  to  the  dense 
mass  of  mesoderm,  which  then  constitutes  the  point  of  union  be- 
tween the  embryonal  formation  and  the  chorion  ectoderm.     This 


Germinal  plate 


Adherent  band 


Extra  embryonal 
area 


Fig.  19a. — Ovum,  Fig.  18a,  after  the  development  of  the  mesodermal  peri- 
embryonal  slit.  (Schematic.)  The  adherent  band  of  mesoderm  connects  the 
embryonal  and  extra-embryonal  divisions. 


point  of  union  contains  the  adherent  band  (future  abdominal 
pedicle)  and  the  caudal  knot  of  the  primitive  streak  (Fig.  19a). 

The  amnion  and  embryo  develop  from  a  small  area  in  the 
germinal  covering,  and  with  the  umbilical  vesicle  are  separated 
from  the  extra-embryonal  area  of  the  ovum,  with  which  they 
are  connected  through  the  adherent  band  of  mesoderm  alone. 
The  embryo  develops  from  a  portion  of  the  ectodermal  lining  of 
the  amnion. 

The  extra-embryonal  area  of  the  ovum  forms  the  troplioblast, 
villi,  the  chorionic  membrane,  and  the  placenta. 


OHAPTEE  V. 
THE    TBOPHOBLAST   IN   THE   OVA  OP   ANIMALS. 

THE  EARLIEST  DEVELOPMENT  OF  THE  ECTODERMAL  EXTRA-EMBRYONAL 
AREA  OF  ANIMAL  OVA. 

In  discussing  the  histology  of  gestation  it  is  important  to  note 
that  in  this  field,  as  well  as  in  that  of  embryology,  many  of 
the  most  important  and  valuable  points  have  been  learned 
through  the  study  of  like  processes  in  animals.  The  results 
obtained  in  investigations  in  the  latter  have  been  applied  more 
or  less  closely  to  the  various  developmental  changes  in  the 
human  being.  Though  ofttimes  erroneously  applied,  they  have 
been  the  source  through  which  many  vexed  questions  have  been 
settled.  More  recent  investigations,  however,  prove  that  it  is 
not  so  much  the  erroneous  applications  of  the  results  gained  in 
the  study  of  animals  as  it  is  errors  made  in  these  observations 
which  have  so  long  delayed  a  satisfactory  conclusion  concerning 
the  various  processes  involved  in  human  placentation.  It  is 
necessary,  for  that  reason,  to  consider  first  the  more  recent 
studies  concerning  animal  placentation,  as  reviewed  by  Strahl. 

Marchand  examined  the  placentas  of  rabbits  gravid  from  eight 
to  sixteen  days.  In  the  earliest  specimens  he  finds  on  the  ovum 
a  growth  of  ectoderm  elements  consisting  of  two  layers:  (1)  a 
deeper  layer  of  separated  cells  and  (2)  a  superficial  plasmodial. 
Since  the  latter  is  still  covered  in  part  by  the  zona,  it  is  neces- 
sarily of  fetal  origin.  In  addition  he  observes  transitions  from 
the  cell  layer  of  the  ectoderm  into  the  plasmodial.  The  deeper 
cells  become  larger  and  are  arranged  in  groups.  Their  cell  boun- 
daries disappear,  and,  through  a  union  of  these  cells,  a  plasmodial 
layer  is  formed,  covering  the  deeper  ectoderm,  but,  as  a  rule, 
distinctly  outlined  from  it.  This  ectodermal  Plasmodium  unites 
with  the  syncytially-changed  uterine  epithelium,  forming  the 
first  connection  between  the  ovum  and  the  uterine  wall.  In  the 
placenta  of  nine  to  ten  days  Marchand  finds  blood  (1)  in  the 
maternal  vessels  possessing  an  endothelial  lining  and  (2)  in  ecto- 
dermal spaces  in  the  cell  layer.  Into  these  spaces,  which  pos- 
sess no  endothelium,  the  blood  from  the  maternal  vessels  enters. 


THE   TROPHOBLAST   IN    THE   OVA   OP   ANIMALS.  47 

In  the  placenta  of  eleven  days  few  of  these  unlined  ectodermal 
spaces  containing  blood  remain.  Most  of  them  are  now  lined 
with  a  continuous  layer  of  elements  rich  in  protoplasm,  which 
Marchand  considers  originate  from  the  maternal  vessel  endo- 
thelium ( ?),  which  has  undergone  a  "syncytial  change." 

Maximow,  in  his  investigations  on  rabbit  placentae,  denies,  in 
contrast  to  Marchand,  the  existence  of  a  fetal  ectodermal  Plas- 
modium as  early  as  the  eighth  day.  He  believes  that,  when  the 
ovum  attaches  itself  to  the  uterine  wall,  the  ectoderm  consists 
of  only  separated  cells,  which  come  in  contact  with  the  epithelium 
of  the  uterus  and  cause  it  to  degenerate.  When  the  ectoderm, 
after  disappearance  of  the  uterine  epithelium,  reaches  the  ma- 
ternal vessels,  the  glycogen-containing  cells  of  the  uterine  con- 
nective tissue  change  to  large  polynuclear  structures.  In  these 
cells  he  finds  elements  resembling  red  blood  cells  in  form  and 
color.  Only  later,  when  the  ectoderm  enters  into  the  decidua, 
does  it  divide  into  two  layers:  (1)  one  with  cell  boundaries,  the 
cytoblast,  and  (2)  one  without  cell  boundaries,  the  plasmodi- 
blast.  The  latter  is  found  only  where  the  villi  come  in  contact 
with  the  glycogen-containing  cells,  at  the  ivalls  of  the  maternal 
vessels.  It  is  not  found  where  the  villi  grow  into  the  connective 
tissue  between  the  vessels.  From  the  tenth  day  on,  spaces  filled 
with  maternal  blood  are  found  in  the  fetal  Plasmodium  and 
there  develops  an  ecto-placenta,  into  ivhose  ectodermal  villous 
formations  the  mesodermal  elements  bringing  the  allantoic  ves- 
sels enter. 

Opitz  finds  in  the  rabbit  a  double  ectodermal  layer  during  the 
process  of  attachment  of  the  ovum  in  the  uterine  wall:  (1)  an 
internal  layer  formed  of  separated  cells,  and  (2)  an  external 
plasmodial  layer.  The  latter  causes  the  uterine  syncytium  to 
disappear  and  aids  the  attachment  of  the  ovum  to  the  uterine 
wall  freed  of  epithelium.  In  the  Plasmodium  spaces  occur  into 
which  maternal  blood  empties  from  the  eroded  maternal  vessels. 
From  the  ovum,  ectodermal  cell  groups  enter  into  this  ectodermal 
Plasmodium,  are  vascularized,  and  later  become  also  plasmodial. 
Those  syncytial  cells  which  Marchand  considers  as  resulting  from 
maternal  endothelium,  Maximow,  however,  views  as  ectodermal 
Plasmodium  when  found  in  the  fetal  portion  of  the  vessels,  but 
considers  them  in  the  maternal  portion  to  be  endothelial.  Opitz 
considers  these  cells  to  be  entirely  of  ectodermal  origin.  It  is 
to  be  noted  that  Maximow  and  Opitz  mention  the  destruction  of 
the  uterine  epithelium.     Later  fetal  mesoderm  with  the  allantoic 


48  THE   TROPHOBLAST   IN   THE   OVA   OP   ANIMALS. 

vessels  enters  into  the  placenta  and  on  its  external  surface  the 
remnants  of  the  ectoderm  are  found  as  flat  covering  cells.  The 
epithelium  of  the  uterus  plays  no  part  in  the  development  of 
the  placenta,  but  forms  a  syncytium  which  is  absorbed  by  the 
ectoderm  cells. 

In  Tarsius,  Hubrecht  finds  that  the  uterine  wall,  through  a 
change  of  the  connective  tissue,  forms  a  trophospongia,  betiveen 
ivhich  the  glands  degenerate.  On  the  growth  of  the  embryonal 
ectoderm  or  trophoblast,  a  mixture  of  trophoblast  and  tropho- 
spongia occurs,  with  a  decided  increase  in  the  volume  of  this 
early  placental  formation.  Then  the  development  of  the  meso- 
dermal villous  elements  takes  place,  and  the  mesoderm  villi 
surround  themselves  with  a  trophoblast  covering.  Between  the 
trophoblast  cells  lacunae  form,  into  which  maternal  blood  passes. 
Finally,  the  trophospongia  becomes  a  thin  layer  which  represents 
the  boundary  toward  the  deeper  maternal  tissue. 

In  Tupaja,  when  the  ovum  rests  upon  the  uterine  wall  its 
ectoderm  causes  the  uterine  epithelium  to  disappear.  The  tro- 
phoblast grows  decidedly,  with  the  formation  of  giant  cells,  and 
occasionally  forms  a  combined  layer  with  the  uterine  epithelium 
in  which  maternal  and  embryonal  nuclei  lie  in  a  common  Plas- 
modium. The  maternal  portions  degenerate,  but  the  ectodermal 
tissue  is  divided  into  ( 1 )  a  deeper  layer,  the  cytotrophoblast,  and 
(2)  a  superficial  syncytial  layer,  the  plasmoditrophoblast,  which 
constitutes  only  a  temporary  differentiation.  In  the  uterine  wall, 
in  the  meantime,  the  connective-tissue  trophospongia  is  formed; 
the  border  between  ectoderm  and  maternal  connective  tissue  dis- 
appears, for  these  tissues  infiltrate  each  other.  In  this  resulting 
union  the  trophospongia  is  overcome  by  the  trophoblast  and  the 
maternal  blood  passes  from  the  maternal  capillaries  into  the  em- 
bryonal trophoblast  spaces.  The  mesodermal  fetal  cells,  then 
enter  with  the  allantoic  vessels  and  receive  on  their  external  sur- 
face a  covering  of  trophoblast. 

Although  various  investigations  have  shown  that  the  variations 
in  the  development  of  the  placenta  in  different  animals  are  quite 
unexpected,  and  that  among  the  individual  mammalia,  even 
when  closely  related,  decided  differences  are  found,  yet  the 
trend  is  more  toward  the  view  that,  as  a  rule,  the  syncytium 
originates  from  fetal  ectoderm.  According  to  Strahl  and  Se- 
lenka,  in  quite  a  group  of  placenta?  the  uterine  epithelium  plays 
no  unimportant  role.  On  the  other  hand,  Frankel,  as  a  result 
of   extensive   investigations,    comes  to   the   conclusion   that   the 


THE    TROPHOBLAST    IN    THE   OVA   OF    ANIMALS.  49 

higher  the  organization  of  the  placenta  and  the  more  firm  the 
connection  between  maternal  and  fetal  tissues,  so  much  the 
less  is  the  maternal  epithelium  preserved. 

He  finds  that  in  the  rodents  and  in  the  insectivorae,  whose  pla- 
centae, of  all  the  animals  he  examined,  stand  nearest  to  the  human 
placenta,  the  uterine  epithelium  ceases  at  the  border  of  the 
placenta.  Only  in  the  pig  does  it  remain.  In  the  cow  and 
sheep  the  epithelium  in  the  cotyledo  shows  a  tendency  to  de- 
generation. In  the  cat,  rabbit,  squirrel,  guinea-pig,  rat,  mouse, 
and  mole  the  uterine  epithelium  takes  no  part  in  the  formation 
of  the  placenta.  A  so-called  syncytial  formation,  however,  he 
finds  to  occur  in  the  most  varying  tissues.  The  higher  in  the 
animal  plane  the  animal  stands,  the  more  does  the  chorionic  epi- 
thelium groiv  into  the  maternal  connective  tissue  robbed  of  its 
epithelium. 

Opitz  finds  that  in  the  guinea-pig  the  foundation  for  the 
placenta  is  the  fetal  ectodermal  plasmodium  vascularized  by 
maternal  vessels.  The  placentae  of  the  rabbit,  the  guinea-pig, 
and  the  human  being  agree  in  that  earlier  or  later  the  ectodermal 
surface  of  the  ovum  comes  in  contact  with  the  connective  tissue 
of  the  uterine  mucosa.  Finally,  between  maternal  blood  and  the 
fetal  vessels  found  in  the  mesoderm  of  the  villi  only  one  layer 
of  the  ectodermal  syncytium  is  left.  The  apparently  great  dif- 
ferences are  to  be  explained  by  the  fact  that  in  the  rabbit  and 
guinea-pig  the  projections  of  ectoderm  and  mesoderm  (the  villi) 
come  into  union  with  each  other,  while  in  the  human  being  they 
are  always  separated. 


CHAPTER  VI. 
THE    TROPHOBLAST    OF    THE    HUMAN    OVUM. 

THE  EARLY  DEVELOPMENT  OP  THE  ECTODERMAL  EXTRA-EMBRYONAL 

AREA. 

Trophoblast. — The  outer  layer  of  the  ovum  consists  of  tropho- 
blast. It  is  a  product  of  the  ectoderm  and  from  it  develop  the 
future  syncytium  and,  according  to  most  authors,  the  cells  of 


E.Z. 


Tr.        Cap.        Bl,L. 


Fig.  20. — Low-power  drawing  of  the  trophoblast,  enveloping  zone,  etc.,  of  an 
ovum  three  days  old.  in  transverse  section.  (Peters.)  Sy.,  syncytium;  F.P., 
plug  of  fibrin  at  the  summit  of  the  capsularis  ;  Bl.L.,  blood  lacunae;  Tr.,  tropho- 
blast ;  M.,  mesoderm ;  Cap.,  capillaries ;  CI.,  glands ;  E.Z.,  enveloping  zone ; 
E.F.,  embryo  formation  ;  Comp.,  compacta  ;   U.E.,  uterine  epithelium  ;   GL,  gland. 

Langhans.  The  "trophoblast,"  according  to  Hubrecht,  "is  the 
epiblast  of  the  blastocyst,  as  far  as  it  has  a  direct  nutritive  sig- 
nificance as  indicated  by  proliferating  processes,  by  immediate 
contact  with  maternal  tissues,  maternal  blood,  or  secreted  ma- 
terial." It  consists  of  small  and  large  cells  of  various  forms. 
Shortly  after  the  ovum  descends  into  the  mucosa  a  connection 


THE  TROPHOBLAST  OF  THE   HUMAN   OVUM.  51 

between  the  trophoblast  and  the  maternal  blood  takes  place.  As 
all  the  capillaries  near  the  trophoblast  consist  of  endothelium 
and  evidence  many  blood  sinuses,  the  trophoblast  is  infiltrated 
with  blood  lacunas  which  are  separated  from  each  other  by 
these  trophoblast  cell  groups.  As  a  result  of  the  growth  of  these 
cells,  of  congestion  and  of  pressure,  the  blood  takes  its  exit 
from  the  capillaries  and  bathes  the  cells.  The  lacunas,  then, 
represent  a  united  system  fed  by  peripheral  capillaries  and  are 
separated  externally  from  the  decidua  by  a  thin  layer  of  ecto- 
dermal trophoblast  cells,  but  the  trophoblast  at  various  points 
may  extend  much  further  into  the  compacta. 

The  ectoblast  cells  are  of  varying  form:  1.  Cubical,  with  large, 
strongly  stained  round  or  oval  nucleus  containing  granules  and 


$%g$0  ;S®$& 


Sy.  Tr. 

.  Fig.  21. — Section  through  the  central  portion  of  the  trophoblast  layer.  The 
trophoblast  {Tr.)  is  covered  with  syncytium  {Sy.)  at  all  points  in  contact  ivith 
the  blood  lacunae    (Bl.L.).     Ekt.,  ectoderm.      (Peters.) 

nucleolus.  2.  These  become  changed.  The  nucleus  becomes 
pale  and  swollen.  Vacuoles  appear  in  the  cells  and  strongly 
stained  fragments  of  the  nucleus  are  evident.  The  cells  are 
irregular  in  form.  3.  The  nuclei  are  larger,  especially  in  the 
external  layers,  and  more  swollen.  The  chromatin  network  is 
irregular  and  dark  lumps  appear  in  the  nucleus.  The  nuclei 
are  of  various  forms,  oval,  spindle-shaped,  and  contain  vacuoles. 
4.  Swollen  groups  of  nuclei  in  degeneration  are  found.  These 
nuclei  contain  one  or  more  nucleoli.  5.  The  protoplasm  of  these 
cells  unites,  forming  protoplasmic  masses  in  the  shape  of  bands 
or  irregular  groups  with  extensions. 


52 


THE  TROPHOBLAST  OP  THE  HUMAN  OVUM. 


From  the  simple  cubical  cells  of  the  central  layer  of  the  tro- 
phoblast we  find,  in  going  toward  the  periphery,  gradual  changes 
from  1  to  5.  The  trophoblast  cells  grow  through  direct  cell 
division.  These  changes  represent  the  results  of  the  corrosive 
action  of  the  Mood  on  these  cells,  whereby  the  future  syncytium 
is  formed.  The  syncytium  then  lines  the  lacunas  (Fig.  22) .  The 
endothelium  of  the  lacunae  and  of  the  capillaries  degenerates 
wherever  it  is  not  lined  by  syncytium.  The  syncytium  is  found 
also  under  the  endothelium  of  the  most  peripheral  trophoblast 


BIL. 


M 


B\  L. 


Pig.  22. — A  capillary  (Cap.)  in  the  serotinal  portion  of  the  trophoblast  in- 
filtrated with  blood  lacunae  (Bl.L.).  The  peripheral  wall  of  the  capillary  is 
preserved  and  forms  the  serotinal  wall  of  the  intervillous  space  at  this  point. 
The  capillary  at  many  points  communicates  with  the  lacunas  (Bl.L.).  In  the 
capillary  is  a  large  mass  of  syncytium  (Sy.)  containing  changed  trophoblast 
nuclei  (a)  and  red  blood  cells  (6).  At  c  changes  in  the  trophoblast  nuclei  are 
evident.  (Peters.)  Tr.,  trophoblast;  EM.,  ectoderm;  M.,  mesoderm;  CO.,  cen- 
tral cavity  of  ovum  ;  p. En.,  peripheral  endothelium. 


masses,  and  proves  that  the  endothelium  plays  no  part  in  tlie 
formation  of  the  syncytium. 

It  is  to  be  noted  that  the  opening  of  the  maternal  vessels  occurs 
at  this  early  stage,  before  villi  are  formed.  The  endothelium 
of  the  capillaries  degenerates  and  the  blood  makes  its  exit  from 


THE  TROPHOBLAST  OF  THE  HUMAN   OVUM.  53 

the  capillaries.  It  ought  to  coagulate,  but  does  not.  It  circu- 
lates against  the  fetal  cells,  which  have  the  power  to  prevent 
coagulation,  and  yet  the  blood  exerts  a  deleterious  influence  on 
these  cells.  Thus  the  resulting  syncytium  lines  the  lacunae,  pre- 
vents coagulation  in  this  primary  intervillous  space  and  later 
about  the  villi,  separating  the  blood  at  all  times  from  the  cells  of 
the  chorionic  centre.  Free  syncytial  cells  are  present,  even  in 
the  vessels  of  the  periphery  in  the  compacta.  At  later  periods 
they  are  found  free  in  the  veins  and  arteries.  It  is  thus  seen 
that  the  cells  of  the  trophoblast  of  the  ovum  enter  the  veins  at  an 
early  period. 

The  Primary  Intervillous  Space  is  intravascular  and  is  bound- 
ed by  maternal  and  fetal  structures.     That  the  developed  inter- 


7\  -^^     ftVA 


Pig.  23. — Change  of  trophoblast  to  syncytium  (Sij.)  The  syncytially  changed 
trophoblast  is  infiltrated  with  numerous  vacuoles  (vac),  c,  red  blood  cells  of 
the  capillary  in  which  this  syncytial  mass  was  floating  attached  by  a  pedicle 
(p).      (Peters.) 

villous  space  contains  free  blood  has  been  granted  by  Virchow, 
Kolliker,  Langhans,  Waldeyer,  etc.  The  drawings  of  Peters 
indicate  a  slowing  and  probable  stagnation  of  the  blood  current. 
The  maternal  endothelium  on  the  side  toward  the  compacta  is 
at  first  intact  and  forms  the  serotinal  wall  of  the  space  (Fig.  22). 
In  it  are  found  isolated  cells  and  groups  of  trophoblast.  Tropho- 
blast cells  are  also  present  on  the  serotinal  wall,  so  that  this  wall 
consists  of  trophoblast,  maternal  endothelium,  and  decidual  tis- 
sue. Later  the  endothelium  of  the  serotinal  side  is  found  only  in 
the  areas  corresponding  to  the  openings  of  the  maternal  vessels. 
Where  the  trophoblast  cells  extend  into  the  enveloping  zone  in 
the  form  of  bands,  uniting  with  each  other  in  a  network,  it  is 


54  THE  TROPHOBLAST  OF  THE  HUMAN  OVUM. 

often  difficult  to  distinguish  between  maternal  and  fetal  cells. 
Merttens  says  the  same.  Thus  the  earliest  ectoderm  cells  enter 
actively  into  the  maternal  tissues. 

The  primary  intervillous  space  is  formed  through  the  gradual 
consumption  of  the  trophoblast.  Through  its  growth  more  and 
more  layers  of  the  compacta  are  included  in  the  enveloping  zone, 
until  the  corrosive  action  of  the  blood  has  furnished  the  villous 
mantle  of  the  ovum.  1.  The  trophoblast  is  reduced  to  a  single 
layer.  2.  The  union  of  the  lacunas  at  first  separated  by  large 
trophoblast  cell  masses  takes  place.  The  origin  and  growth  of 
the  intervillous  space  thus  goes  hand  in  hand  with  the  various 
steps  leading  to  the  formation  of  villi.  In  the  ovum  of  Peters 
no  villi  are  yet  present.  The  inner  surface  of  the  trophoblast 
shows  irregular,  finger-like  depressions  into  which  mesoderm  is 
beginning  to  enter.     The  lacunas  have  enlarged  and  the   cell 

M.      ■ 

Tr.     .._ 3^i    '       '"'--.. 


Fig.  24. — Schematic  representation  of  the  earliest  stage  of  the  development  of 
the  placenta.  (Peters.)  M.,  mesoderm;  Tr.,  trophoblast;  Bl.L.,  blood  lacunae; 
Sy.,  syncytium ;  En.,  endothelium  ;  Cap.,  capillary  ;  E.Z.,  enveloping  zone ;  Sp., 
spongiosa. 

masses  between  them  have  become  smaller.  Through  the  entrance 
of  the  growing  mesoderm  into  these  divided  cell  masses,  which 
are  finally  reduced  by  the  blood  to  the  syncytial  layer,  villi  are 
formed  and  the  primary  intervillous  space  becomes  larger.  The 
primary  enveloping  zone  becomes  the  subsequent  intervillous 
space. 

The  maternal  endothelium  breaks  down  and  is  found  floating 
in  the  lacunas.  It  is  never  seen  in  a  proliferating  stage.  Syn- 
cytium is  found  under  it.  It  is  impossible  for  the  endothelium 
to  fill  out  all  the  spaces  of  the  trophoblast,  and,  if  it  did  do  so, 
we  ought  to  see  it  somewhere  in  the  process  of  growth.  On  the 
contrary,  it  is  always  seen  to  degenerate.  Therefore  the  syn- 
cytium does  not  originate  from  maternal  endothelium. 


THE  TROPHOBLAST  OF  THE  HUMAN  OVUM.  55 

The  syncytium  is  found  over  the  surface  of  the  ovum,  in  the 
trophoblast,  in  the  lacunae,  toward  the  enveloping  zone,  and  also 
in  the  periphery  of  the  ectodermal  trophoblast.  At  the  summit 
of  the  ovum  syncytium  is  also  present.  In  numerous  points  the 
direct  transition  from  trophoblast  cells  to  syncytium  is  distinctly 
seen.  Therefore  it  does  not  originate  from  the  uterine  epithe- 
lium. 

The  glands  in  the  decidua  about  the  ovum  become  filled  with 
blood.  They  are  pushed  aside  by  the  growing  ovum  and  are 
broken  into  by  the  trophoblast  and  syncytium.  Their  epithe- 
lium degenerates  and  disappears.  The  uterine  epithelium  plays 
no  part  in  the  formation  of  the  syncytium. 

The  syncytium  consists  of  a  shining,  granular  protoplasm  con- 
taining numerous  nuclei.  The  nuclei  are  round,  oval,  or  flat- 
tened. There  are  also  vacuoles  in  the  protoplasm,  which  make 
the  latter  appear  like  septa  in  which  are  flat  and  half-moon- 
shaped  nuclei  (Fig.  23). 

Van  Siegenbeck  finds  syncytial  giant  cells  especially  near  the 
union  between  maternal  and  fetal  tissues,  in  and  about  the 
lacuna?,  between  the  ectoblast  and  the  compacta,  covering  the 
free  compacta,  about  the  maternal  capillaries,  and  even  more 
externally  in  the  vessels.  He  finds  a  gradual  transition  from 
trophoblast  to  syncytium.  In  one  place  he  observed  a  syncy- 
tial giant  cell  between  the  mesoblast,  and  the  ectoblast  of  the 
fetal  sac,  which  he  considers  as  a  proof  of  the  ability  of  these 
cells  to  wander  into  surrounding  tissues. 

The  processes,  so  far,  are  well  represented  in  the  schematic 
drawing,  Fig.  24. 

Merttens  found  in  the  particles  obtained  by  curetting  sixteen 
days  after  the  last  menstruation  a  few  sections  of  an  ovum  with 
the  enveloping  decidua.  He  describes  (1)  the  chorion  and  the 
villi ;  on  the  latter  are  cell  groups,  and  between  them  are  found 
spaces  constituting  the  intervillous  space;  (2)  the  spongiosa, 
containing  numerous  glands,  and  (3)  the  compacta,  a  pale  zone 
lying  between  1  and  2,  and  containing  large  pale  cells  between 
which  are  numerous  darkly-stained  nuclei. 

In  the  compacta  he  finds  large  cells  and  large  spaces.  Be- 
tween the  large  cells  syncytial  masses  are  irregularly  distributed. 
The  cell  spaces  are  round,  long,  or  irregular,  and  often  empty 
into  the  intervillous  space.  They  contain  blood  and  are  all  lined 
with  syncytial  masses,  which  at  some  points  are  very  thin,  and 
at  other  points  quite  thick.     Where  these  spaces  empty  into  the 


56  THE  TROPHOBLAST  OP  THE  HUMAN   OVUM. 

intervillous  space  the  syncytial  masses  continue  into  the  syn- 
cytium of  the  villi.  Merttens  does  not  know  whether  these  spaces 
are  glands,  vessels,  or  lymph  spaces.  They  are  possibly,  however, 
the  lacunae  ~of  Hubrecht  and  Peters. 

The  epithelia  of  the  glands  are  like  beaker  cells,  and  on  their 
free  tips  is  a  half -moon  of  glycogen.  The  glands  evidence  papil- 
lary projections  (compare  Fig.  14ft).  Merttens  believes  that  the 
syncytium  results  through  a  change  of  the  surface  and  gland 
epithelium  ( ?).  In  his  Fig.  8  Merttens  represents,  in  the  upper 
portion,  the  epithelium  of  such  a  gland,  and  the  lower  half  repre- 
sents syncytial  masses.  He  believes  that  the  latter  results  from 
these  epithelial  cells,  which  lose  their  cylindrical  form  and  unite. 
From  his  description  and  his  drawings  it  is  neither  clear  nor 
probable  that  the  epithelium  goes  over  into  these  syncytial  masses. 
Besides,  this  area  is  taken  from  decidua  particles  not  connected 
with  the  ovum,  and  at  no  point  can  he  find  the  epithelium  of  the 
glands  contributing  in  any  way  to  the  syncytium  of  the  chorion. 

On  the  contrary,  this  ovum  is  at  the  stage  where  the  tropho- 
blast  is  almost  consumed  by  the  growth  of  the  intervillous  space, 
and  the  cell  groups  at  the  end  of  the  villi,  which  Merttens  calls 
points  of  union  between  the  villi  and  the  decidua,  are  really 
the  remains  of  the  trophoblast  (Fig.  31). 


CHAPTER   VII. 
THE  FURTHER  DEVELOPMENT  OP  THE  HUMAN  OVUM. 

THE  EARLY  DEVELOPMENT   OF   THE  EMBRYONAL  AREA. 

1.  The  ovum  v.  H.,  described  by  Spee,  was  thrown  off  after  five 
weeks  menopause.  The  ovum  contains  an  oval  germinal  plate 
entirely  in  the  stage  of  the  primitive  streak  and  situated  in  the 
wall  of  the  amniotic  cavity.  The  entire  embryonal  formation  is 
0.4  millimetre  long.  The  greatest  diameter  of  the  ovum  in- 
cluding the  villi  is  5%  to  7  millimetres.  Under  the  chorion  was 
found  a  thin  layer  of  connective  tissue  poor  in  cells  and  bounding 
directly  the  mesodermal  slit.  From  this  layer  the  chorion  could 
be  lifted  off.     The  inner  part  of  the  ovum  contained  a  bubble  of 

Chorionic  villi 


Amnion 
Membrana  chorii 

,    Adherent  band  or 
Entoderm  yolk  vesicle  -  r'A  vvrftjf  abdominal  pedicle 

\ 

Transverse  furrow 

Fig.  25. — Ovum  v.H.  (Spee),  showing  embryonal  and  extra-embryonal  areas. 
The  extra-embryonal  villi  and  membrana  chorii  are  connected  with  the  embryonal 
formation  by  the  adherent  band  of  mesoderm. 

air  and  a  non-celled  fibred  coagulation  substance  in  which,  on  the 
serotinal  side,  was  seen  the  embryonal  formation,  which  in- 
cluded the  amniotic  cavity  with  the  germinal  plate  and  the 
umbilical  vesicle  (Fig.  25). 

The  primitive  streak  region  is  small,  and  yet  the  development 
of  mesoderm  within  the  chorion,  in  the  abdominal  pedicle  and 
about  the  amniotic  cavity  and  about  the  umbilical  vesicle,  is  so 
great  that  considerable  time  must  have  been  needed  for  its  de- 
velopment. At  the  time  when  the  mesoderm  began  to  develop, 
the  ovum  was  probably  of  a  diameter  of  0.5  millimetre.  At  the 
first  beginning  of  the  mesoderm  slit  the  ovum  was  probably  of  a 
diameter  of  1  millimetre. 

The  embryonal  formation  is  a  long,  thick  projection  connected 


58 


FURTHER   DEVELOPMENT   OP    THE   HUMAN    OVUM. 


at  one  end  with  the  inner  side  of  the  chorion,  but  otherwise  pro- 
jecting free  into  the  cavity  of  the  vesicle,  that  is,  the  periem- 
bryonal  mesoderm  slit  (Fig.  25).  A  superficial  transverse  fur- 
row divides  it  into  two  elliptical  parts.  The  larger  is  at  the  free 
end  and  contains  the  entoderm  vesicle.  The  smaller  part  con- 
tains the  amniotic  cavity  lined  with  ectoderm  and  consists,  in 


A>\ 


Pig.  26. — Longitudinal  section  through  Pig.  25,  ovum  v.H.  of  Spee.  V.V.,  the 
future  umbilical  vesicle.  The  adherent  band  of  mesoderm  connects  the  embryonal 
formation  with  the  extra-embryonal  membrana  chorii. 

addition,  of  the  compact  band  of  mesoderm  which  covers  three- 
fourths  of  the  amnion,  from  the  mesodermal  covering  of  the 
entoderm  vesicle  up  to  the  chorion  (Fig.  26) .  This  compact  band 
is  the  adherent  pedicle  and  corresponds  to  the  caudal  end  of  the 
primitive  streak.  The  entoderm  vesicle  sends  a  blind  duct,  lined 
with  entoderm,  into  the  adherent  pedicle.     The  entoderm  vesicle 


Germinal  plate 


Pig.  27. — Pig.  26  enlarged,  showing  actual  conditions  in  the  ovum  v.H.  pic- 
tured schematically  in  Pig.  19a.  U.V.,  the  future  umbilical  vesicle  ;  ENT.,  ento- 
derm ;  HES.,  mesoderm. 

lined  with  a  single  row  of  cubical  cells,  and  covered  with  meso- 
derm, is  the  umbilical  vesicle.  The  amniotic  cavity  is  lined 
with  ectoderm  and  is  likewise  covered  with  mesoderm.  The 
single  layer  of  flat  cells  lining  the  amniotic  cavity  begins  to 
thicken  at  a  certain  point ;  the  cells  become  high  cylindrical  and 
constitute  the  germinal  plate.    That  part  of  the  ectoderm  of  the 


FURTHER   DEVELOPMENT    OF    THE   HUMAN    OVUM. 


59 


amniotic  cavity  lying  on  the  umbilical  vesicle  enters,  then,  into 
the  formation  of  this  thick  germinal  plate.  The  mesoderm  which 
covers  the  umbilical  vesicle  and  the  amnion  unites  in  the  narrow 
zone  which  separates  the  two.  Here  where  the  walls  of  the  um- 
bilical vesicle  and  amnion  run  parallel,  the  germinal  plate  is 
found  on  the  inner  surface  of  the  amniotic  cavity.  From  the 
caudal  knot  up  to  the  chorion  extends  the  adherent  pedicle,  the 
future  abdominal  pedicle,  and  here  the  mesoderm  lining  the 


Mesoderm 


Fig.    28. — Transverse    section    through    germinal    plate    of    Figs.    26    and    27 
(Spee.) 


chorion  and  that  found  in  the  embryonal  formation  unite  (Figs. 
26,  27). 

Posterior  to  the  caudal  knot  of  the  germinal  plate,  the  um- 
bilical vesicle  sends  a  prolongation,  the  allantoic  duct,  into  the 
abdominal  pedicle,  which  duct  is  separated  from  the  caudal  side 
of  the  amnion  by  mesoderm.  It  is  relatively  long  and  probably 
formed  early.  It  is  through  the  adherent  band  of  mesoderm  that 
the  vessels  of  the  fetus  pass  to  the  chorionic  membrane  and  into 
the  villi. 

The  caudal  knot  of  the  primitive  streak  region  forms  the  ab- 


60 


FURTHER    DEVELOPMENT    OF    THE    HUMAN    OVUM. 


dominal  pedicle.  The  germinal  plate  is  only  a  portion  of  the 
completed  primitive  streak  region.  There  is  as  yet  no  differ- 
entiation into  medullary  plates  or  chorda.  The  germinal  plate 
has  its  dorsal  surface  toward  the  point  of  union  of  the  abdominal 


Germinal  plate 


Fig.  29. — Change  from  Fig.  27,  showing  ventral  curve  due  to  growth  in  length 
of  germinal  plate.     (Schematic.)     M,  mesoderm. 

pedicle  to  the  chorion  and  its  long  axis  runs  radially  to  the 
chorion.  It  is  of  oval  form  and  has  a  median  furrow  on  its 
dorsal  surface.     Its  dorsal  surface  follows,  in  addition,  the  curve 


*#£k 


Allantoic  duct 


Fig.   29a. — Stage   of  still   further   growth   of   cephalic   end   of  germinal   plate. 
Embryo  Gle  of  Spee. 

of  the  amniotic  cavity  and  is  therefore  concave.  Its  dorsal  fur- 
row lies  in  the  same  plane  as  the  lumen  of  the  allantoic  duct,  and 
its  caudal  portion  is  at  right  angles  to  the  duct.  It  consists  of 
high  cylindrical  cells,  highest  at  the  middle  (Fig.  28).     Laterally 


FURTHER   DEVELOPMENT    OF    THE    HUMAN    OVUM. 


61 


it  extends  on  into  the  amniotic  lining.  Laterally,  ectoderm  and 
mesoderm  are  separated  by  a  membrana  prima,  which  is  always 
present  between  parallel  layers  of  mesoderm  and  ectoderm.  In 
the  median  line,  however,  is  a  fibred,  granular  substance,  and 
here  possibly  a  connection  between  ectoderm  and  mesoderm  ex- 
isted. A  characteristic  connection  at  the  region  of  the  primitive 
streak  is  present  in  mammalia  and  in  older  human  embryos. 
There  is  probably  no  connection  between  mesoderm  and  ento- 
derm, and  in  the  next  embryo  there  is  no  layer  continuity  be- 

Vanalis  neurenterious 


Ectoderm 


Allantoic  duct 


Blood  islands 


Fig.  29b. — Embryo  Glc  of  Spee.  A,  amnion  cavity.  X,  between  ecto- 
derm and  entoderm  mesoderm  comes.  All  anterior  to  the  canalis  neurentericus 
is  new  as  compared  with  embryo  v.H.,  Fig.  27. 


tween  mesoderm  and  entoderm  posterior   to  the   canalis  neu- 
rentericus. 

It  is  to  be  noted  that  in  Fig.  27  the  germinal  plate  has  a 
dorsal  curve.  The  next  stage  is  represented  by  a  ventral  curve 
(Fig.  29).  As  a  result  of  this  (1)  the  mesoderm  between  the 
germinal  plate  and  the  entodermal  vesicle,  and  (2)  that  part  of 
the  entodermal  vesicle  lying  parallel  to  the  germinal  plate  he- 
come  included  in  the  ventrum  of  the  curved  germinal  plate  and 
form  the  mesoderm  and  entoderm  of  the  fetus.  The  actual 
change  is  seen  in  Fig.  29  a  and  o. 


b'Z  FURTHER   DEVELOPMENT   OP    THE   HUMAN    OVUM. 

2.  The  next  older  embryo  (Gle)  shows  that  the  new  growth  con- 
cerns the  addition  of  new  elements  to  the  germinal  plate,  plus  an 
increase  in  the  size  of  the  amniotic  cavity  and  the  umbilical  vesicle 
(Fig.  29&).  ,The  primitive  streak  region*in  v.  H.  has  grown  a  lit- 
tle, but  keeps  its  position  approximately.  The  mesoderm  of  the 
abdominal  pedicle,  the  allantoic  duct,  and  the  caudal  part  of  the 
primitive  streak  region  remain  about  the  same.  In  their  growth 
a  pause  ensued,  which  pause  continues  until  the  embryo  has  seven 
primary  vertebra?.  Therefore  the  added  growth  concerns  the 
cranial  end  of  the  germinal  plate,  while  the  caudal  end  remains  a 
fixed  point.  The  anterior  part  of  the  germinal  plate  has  grown 
to  four  times  the  size  of  that  in  v.  II.,  with  the  result  that  it  ex- 
tends almost  at  right  angles  to  the  original  germinal  plate,  be- 
cause the  caudal  end  remained  a  fixed  point  and  thus  caused  a 
transposition  of  the  cranial  area  of  the  germinal  plate.     Thus 


Amniot. 
mesoderm . 


Amniot.      

ectoderm. 


Umbil.   ves-        V.  :*'y        4' 

iclc  meso-    — -%f   %.:>'' 

derm.  \  ,-,' 

\  % 

Pig.  30. — The  three  layers  of  a  human  embryo,  still  without  primary  ver- 
tebrae. Transverse  section.  (Keibel.)  Showing  growth  of  lateral  walls,  which 
thus  enclose  the  entoderm  within  them. 

the  umbilical  vesicle  and  amniotic  cavity  are  pushed  away  from 
their  position  near  the  chorion  into  the  deeper  part  of  the  meso- 
dermal slit.  A  continuation  of  this  process  causes  the  embryo 
eventually  to  lie  with  its  ventral  surface  turned  toward  the  point 
of  adhesion  of  the  abdominal  pedicle.  At  the  same  time  the 
umbilical  vesicle  has  grown,  too,  so  that  the  embryonal  formation 
of  Gle  has  added  a  growth  almost  as  large  as  v.  H.  itself.  In 
v.  H.  all  those  areas  of  the  germinal  plate  are  absent  which  in  Gle 
turn  their  dorsal  side  to  the  chorion,  that  is,  all  cranial  to  a  line 
drawn  transversely  through  the  canalis  neurentericus  (Fig.  295). 
The  germinal  plate,  as  a  result  of  the  rapid  growth  of  the 
medullary  plates,  grows  at  right  angles  to  the  long  axis  of  the 
primitive  streak  region  of  v.  H.  The  primitive  furrow  has  an 
S  shape  on  the  dorsal  surface.  The  cranial  end  of  the  chorda 
formation  bends  ventrically  and  ends  together  with  the  anterior 
end  of  the  medullary  plate.     Anterior  to  the  canalis  neurenteri- 


■SN 

i$v\. 

Ectoderm 

ir*--f  "' 

\  \ —   Mesoderm 

H 

./;'(r~~  Mesoderm  division 

',. ;  '.--v 

5    1 

r---f—  Entoderm 

FURTHER   DEVELOPMENT   OP    THE   HUMAN    OVUM. 


63 


cus  the  chorda  entoderm  and  the  medullary  plate  lie  close  to- 
gether.    At  the  anterior  boundary  of  the  canalis  neurentericus 


Ectoderm 

Parietal   mesoderm 
Visceral  mesoderm 


Entoderm  .. 


■■•■   Medullar1}/   canal 

—   Intestine 
—    Celom 

Vmb.vesicle 


Fig.  30a. — The  forming   of  the   intestine.        Schematic.  (Kollmann.)        The 

mesoderm  is  divided  into  a  parietal  and  a  visceral  layer.  The  celom,  or  space 

between  these  layers,  is  the  future  peritoneum.     Intestine  and  umbilical  vesicle 
are  connected  by  a  narrow  duct. 

the  ectoderm  bends  into  the  area  of  the  chorda  entoderm  and  the 
latter  possesses  elements  of  the  ectoderm. 

With  the  continued  growth  of  the  cephalic  end  and  the  conse- 


•Oral  space 

1  Branchial  arch 

2  Branchial  arch 

Parietal  wall  of 
m  esoderm 

Celom  1 
Anterior  intestine 


Middle  intestine 
and  umbilical 
vesicle 


Celom  2 
End  intestine 


Abdominal  pedicle 


Pig.  30b. — Human  embryo,  2-4  millimetres  long,  with  heart  and  abdominal 
vesicle  removed  and  umbilical  pedicle  cut.  (After  His.)  Showing  connection  be- 
tween intestine  and  umbilical  vesicle. 

quently  decided  ventral  curve  of  the  embryo,  as  well  as  through 
the  growth  of  the  lateral  walls,  a  portion  of  the  entodermal  sac 
lies  within  the    embryo.     The    ectodermal    germinal  plate  has 


64 


FURTHER   DEVELOPMENT    OF    THE    HUMAN    OVUM. 


on  its  ventral  surface  then  a  strip  of  mesoderm  and  upon  this 
mesoderm  a  part  of  the  very  entoderm  which  lines  the  entodermal 


a.  umh.  d. 


Allantoic  duct 
Cloacal  membrane  r 


Celom.  Aorta 


Schw, 


Chorda 


Fig.  30c. — Caudal  end  of  embryo,  3  mm.  long.  Reconstruction.  (Keibel.)  CI., 
cloaca  :  Md..  medullary  canal ;  Seine,  tail ;  Schw.  D.,  caudal  intestine.  Showing 
relation  of  allantoic  duct  to  the  cloaca. 

abdominal  vesicle  (Fig.  30).  Anterior  to  the  canalis  neuren- 
tericus  is  found  most  of  the  embryo  and  the  medullary  farrow 
and  plates.     The  embryo  consists  here  of  three  layers. 

Allantoic 
duct 

Cloaca 


Fig.  30d. — Embryo  296,  with  decided  ventral  curve,  has  turned  so  that  the  ab- 
dominal surface  faces  the  adherent  band.  X,  omphalo-enteric  duct.  The  heavy 
black  line  about  A,  passing  off  from  either  end  of  the  embryo,  is  the  amnion.  Int., 
Intestine.  Umb.  pes.,  umbilical  vesicle.  (Schematic.)  The  embryo  now  has  its 
ventral  surface  turned  toward  the  abdominal  pedicle. 


Posterior  to  the  canalis  neurentericus  is  the  original  primitive 
furrow  with  the  primitive  lateral  plates.     The  embryo  here  con- 


FURTHER  DEVELOPMFNT  OF  THE  HUMAN  OVUM.  65 

sists,  too,  of  three  layers.  The  mesoderm  of  the  posterior  part  goes 
over  into  the  adherent  mesodermal  band,  the  future  abdominal 
pedicle.  At  the  anterior  and  posterior  ends  the  ectodermal  layer 
of  the  embryo  goes  over  into  the  single-layered  amnion. 

The  original  cephalic  and  caudal  ends  of  the  embryo  (the 
points  where  ectodermal  germinal  plate  goes  over  into  single- 
layered  amnion)  develop  decided  ventral  curves.  So  do  the  lat- 
eral walls  or  sides  of  the  germinal  plate.  As  a  result,  the  ab- 
dominal vesicle  becomes  constricted  more  and  more,  and  the  wide 
connection  of  the  abdominal  vesicle  with  the  entodermal  area  of 
the  embryo  is  narrowed  so  that  a  constantly  narrower  portion  con- 
nects the  abdominal  vesicle  with  the  interior  of  the  embryo  (Fig. 
30a).  The  portion  in  the  embryo,  the  entoderm  of  the  embryo, 
forms  the  intestine  and  the  cloaca  (Fig.  30  a  and  b.  The  cloaca  is 


Vesicle 

P' 

pf 

-  Medullary  plates 

Neur ■enteric,  canal- 

V 

V 

Primitive  furrou- 

Cauda  or  tail 

X 

— \  7~ 

w£r Cloacal  membrane 

Fig.  30e. — External  scheme  of  embryonal  formation,  caudal  end,  with  amnion 
removed,  showing  relative  situation  of  parts.  A  combination  of  Figs.  29b  and 
30c.     (Waldeyer.) 

a  sac  into  which  intestine  and  allantoic  duct  enter  (Fig.  30c). 
As  a  result  the  abdominal  vesicle  is  connected  with  the  intestine 
by  what  has  become  a  narrow  duct,  the  omphalo-enteric  duct, 
while  the  allantoic  duct  situated  in  the  adherent  band  enters  the 
cloaca  (Fig.  30d).  It  may  be  said,  for  the  sake  of  a  readier  un- 
derstanding, that  the  cloacal  portion  of  the  entoderm  sends  a 
prolongation,  the  allantoic  duct,  into  the  adherent  band.  (On 
the  umbilical  vesicle  develop  vessels,  the  omphalo-mesenteric  ves- 
sels, which  enter  the  mesentery  of  the  intestines,  while  the  om- 
phalo-enteric duct  enters  the  intestine  near  the  future  cecum.) 
Later  the  cloaca  becomes  divided  into  a  posterior  part  continuous 
with  the  intestine,  the  rectum,  and  an  anterior  part,  or  bladder, 
continuous  with  the  allantoic  duct,  the  future  urachus. 
.  5 


OHAPTEE  Till. 
THE    CHORIONIC    VILLI. 

EARLY  DEVELOPMENT. 

The  ectodermal  cover  of  the  ovum  has  the  name  chorion-ecto- 
derm  to  distinguish  it  from  the  ectoderm  in  the  amniotic  cavity, 
a  part  of  which  takes  part  in  the  embryonal  formation. 

This  ectodermal  cover  evidences  a  great  growth  of  cells  in  the 
entire  circumference  of  the  ovum,  forming  what  is  called  the 
trophoblast.  These  trophoblast  cells  invade  the  decidual  com- 
pacta.  The  capillaries  of  the  compacta  dilate  into  lacunae  or 
wide  spaces.  The  blood  breaks  through  the  lacuna?  and  now, 
at  this  early  time,  maternal  blood  comes  in  contact  with  fetal 
ectodermal  trophoblast  cells.  The  maternal  blood  when  it  comes 
into  contact  with  the  trophoblast  cells  changes  them  to  large  poly- 
nuclear  cells,  consisting  of  the  protoplasm  of  several  cells  in 
which  the  trophoblast  nuclei  of  these  cells  form  a  polynuclear 
group.  Such  groups  and  likewise  large  mononuclear  cells  result 
from  the  action  of  the  blood  on  the  trophoblast.  Such  resulting 
cells  are  called  syncytial  cells,  mononuclear  or  polynuclear. 
They  line,  too,  the  lacuna?  in  the  circumference  of  the  tropho- 
blast. 

The  trophoblast  cells  are  constantly  spreading  in  the  periphery 
of  the  ovum,  entering  further  and  further  into  the  decidua. 
They  have  a  destructive  action  on  the  decidual  cells ;  they  reach 
capillaries  and  vessels  and  enter  the  latter.  Wherever  they  open 
lacuna?  or  vessels  the  outpoured  blood  changes  the  trophoblast 
cells  with  which  it  comes  in  contact  into  syncytium.  As  a  result 
the  trophoblast  is  divided  and  subdivided  into  small  islands  con- 
sisting of  groups  and  masses  of  trophoblast  cells.  The  cells  on 
the  outside  of  these  groups  are  changed  by  blood  to  syncytium. 
Such  groups  of  trophoblast  cells  surrounded  by  syncytium  are 
the  future  villi.  Subsequently  mesoderm  develops  in  the  interior 
of  these  trophoblast  islands  or  ' '  cell  groups ' '  and  we  have  young 
villi  (Fig.  31).  Later  most  of  the  trophoblast  cells  are  displaced 
and  disappear  with  the  exception  of  a  single  row  situated  imme- 
diately beneath  the  syncytium.  This  single  row,  composed  of 
large  distinct  cells  with  pale  protoplasm  and  large  nuclei,  is  called 


THE  CHORIONIC  VILLI. 


67 


the  cell-layer  of  Langhans.  In  the  centre  of  such  groups  is  thy 
developed  mesoderm,  and  the  so-called  villi  are  now  formed,  but 
as  yet  no  capillaries  are  present.  Such  extensions,  composed  of  a 
centre  of  mesoderm  and  a  periphery  of  Langhans  cells,  with  the 
latter  surrounded  by  syncytium,  are  the  final  villi  in  whose  con- 
uective-tissue  centre  capillaries  finally  develop  which  are  con- 
nected with  the  capillaries  of  the  fetus. 

When  the  trophoblast  first  develops  and.  extends  into  the  ma- 
ternal compacta  its  margin  is  irregular  and.  serrated  (Fig.  20). 
As  capillaries  on  the  compacta  are  opened  syncytium  is  formed 
wherever  blood  touches  the  trophoblast  cells.  The  points  of  tro- 
phoblast furthest  advanced  extend  continually  into  new  com- 
pacta, destroy  it,  and  open  more  capillaries.     In  this  way  the 


Mesoderm. 


Fetal  capillaries. 

Trophoblast. 

Deci6.ua. 

Mat.  capillary. 

Endothelium. 


Mat.  lacuna.  Fibrin.  Intervillous  space. 

Fig.  31. — Schematic  representation  of  a  later  stage  of  placental  development 
than  Fig.  24,  showing  young  villi.     (Peters.) 

process  is  carried  on  through  a  constantly  increasing  periphery. 
As  a  result  long,  irregular,  branching,  finger-like  extensions  of 
trophoblast  project  out  from  the  trophoblast  layers  situated  im- 
mediately on  the  external  layer  of  mesoderm  produced  by  the 
mesoderm  slit.  These  layers  are,  too,  changed  to  syncytium  and 
cell  layer  of  Langhans.  Under  them  the  mesoderm  also  grows 
and  displaces  most  of  the  trophoblast  cells.  The  resulting  con- 
tinuous outer  wall  of  the  ovum  from  which  the  finger-like  ex- 
tensions (villi)  project  is  called  the  membrana  chorii  (Figs.  25, 
27,29,  296,  3(M). 

To  the  inner  surface  of  the  membrana  chorii  is  attached  the 
adherent  band,  or  abdominal  pedicle.  It  is  a  band  of  mesoderm 
which  has  grown  continually  longer.  In  it  is  the  allantoic  duct. 
Through  it  pass  the  vessels  of  the  fetus  to  enter  the  mesoderm  of 
the  membrana  chorii  and  the  mesoderm  of  the  villi. 


68  THE  CHORIONIC  VILLI. 

The  capillaries  which  develop  in  the  villi  unite  with  the  vessels 
of  the  fetus  in  the  membrana  chorii.  Thus,  through  the  medium 
of  the  adherent  band,  fetal  blood  is  brought  into  the  villi.  The 
villi  are  surrounded  by  maternal  blood  and  so  an  exchange  be- 
tween fetal  and  maternal  blood  is  carried  on  through  the  two 
layers  of  epithelium  covering  the  villi  (Fig.  31). 

In  the  Fourth  Week  of  Uterine  Gestation,  when  the  original 
trophoblast  capsule  is  consumed,  the  ovum  is  loosely  connected 
ivith  the  decidua  by  only  a  few  adherent  villi.  The  following 
remarks  concern  such  an  ovum,  covered  with  chorionic  villi, 

Layer  of  Langlians. 

Stroma  and  nucleated 
red  blood  cells. 


Syncytium. 


Cell  group  or  pillar 
at  tip  of  villus. 


Pig.  31a. — A  well-developed  villus  showing  cell  layer  of  Langlians  with  "cell 
group  or  pillar"  at  its  tip.  These  cell  groups  are  trophoblast  cells.  The  villus 
is  covered  with  syncytium  which  is  very  thin  over  the  "cell  group." 


aborted  in  the  fourth  week.  Its  attachment  in  the  uterus  must 
have  been  exceedingly  loose,  for  the  numerous  and  countless  villi 
connected  with  the  covering  of  the  ovum  carried  with  them  no 
decidua  cells.  It  was  hardened  in  alcohol,  cut  in  series  sections, 
and  stained  with  hematoxylin  and  eosin.  Examination  showed 
a  point  of  rupture  in  the  wall  through  which  the  fetus  had  been 
expelled. 

The  important  points  with  regard  to  the  villi  are  as  follows: 
In  a  well-developed  villus  (Fig.  31a)  we  find  a  connective-tissue 
centre  made  up  of  long,  thin,  and  branching  cells  situated  in  a 


THE  CHORIONIC  VILLI. 


69 


basis  composed  of  a  finely  granular,  frothy,  and  often  red-stain- 
ing substance  like  that  found  in  the  fetal  sac.  On  this  connec- 
tive-tissue centre  is  a  single  layer  of  large,  sharply  outlined 
mononuclear  cells  forming  a  continuous  covering  of  the  same. 
This  layer  frequently  forms  groups  at  the  tips  of  the  villi 
(Fig.  31a).  This  layer,  the  so-called  layer  of  Langhans,  is  com- 
posed of  large  round  or  polygonal  cells  with  a  pale,  almost  water- 
clear,  protoplasm  poor  in  granules.  The  nucleus  is  large,  round, 
and  homogeneous  and  generally  contains  one  nucleolus.     The 


i  .Syncytium.. 


... 


Syncytium. 

% 

Membrana  chorii. 


a/.  *;     A.  '  •       * 
y  ifi*~i .  ,  *j.  VI  /**S  . . 


.7  >fti: 


.V> 


,„^^«-** 


Fig.  316. — An  outgrowth  on  the  membrana  chorii  containing  trophoblast  cells 
in  the  lower  portion,  and  showing  the  various  changes  to  distinct  Langhans 
cells  in  the  centre,  and  especially  to  syncytium  and  syncytial  masses  on  contact 
with  maternal  blood  in  the  periphery. 


layer  of  Langhans  is  separated  from  the  stroma  of  the  villus  by  a 
sharp  outline.  The  side  away  from  the  mesoderm  is  smooth  ami 
covered  by  a  distinct  structureless  membrane.  The  outer  syncy- 
tial covering  is  a  thin  layer  of  protoplasm  containing  a  single 
row  of  dark  nuclei.  In  the  stroma  of  these  villi  may  be  seen 
round  spheroidal  trophoblast  cells,  and  their  change  into  nu- 
cleated red  blood  cells  can  be  readily  observed. 

The  younger  villi   and  the  large   cell   groups  which  repre- 


70  THE  CHORIONIC  VILLI. 

sent  the  early  formative  stages  of  villi  possess  the  same  structure 
and  cells  as  the  outgrowths  found  on  the  external  surface  of  the 
membrana  chorii  (Fig.  316).  "We  find  villi  composed  entirely  of 
spheroidal  trophoblast  cells  surrounded  by  a  covering  of  syncy- 


<s5Jl3Sfi*i^  &*;•<>. 


Fig.    32. — Villus    composed   of   trophoblast    cells    showing    transitions    to    the 
syncytial  covering  aDd  to  syncytial  groups  on  the  left. 

tium.  The  gradual  transition  from  these  trophoblast  cells  into 
syncytium,  and  the  change  of  the  trophoblast  nuclei  into  the 
nuclei  of  the  syncytium,  can  be  distinctly  observed  (Figs.  315  and 
32).     Other  villi  are  composed  of  trophoblast  cells  with  a  distinct 


r  &    - 


*3 


S5B-  » 

6 


? 


Wi"'";*r"     ~     ■    &.    e --.  •=' 


'a& 


Fig.    32a. — Villus    composed    of   trophoblast    cells    with    distinct    large    proto- 
plasm. 


protoplasmatic  body  (Fig.  32a).  The  trophoblast  nuclei  pre- 
serve their  pronounced  spheroidal  form.  The  syncytial  covering 
is  at  numerous  points  possessed  of  more  than  a  single  layer  of 
nuclei  and  sends  extensions  into  the  trophoblast  centre.  Other 
villi  composed  of  trophoblast  nuclei  possess  a  beginning  centre  of 


THE  CHORIONIC  VILLI.  71 

mesoderm  (Fig.  33).  The  syncytial  covering  contains  vacuoles 
in  the  wall  of  which  are  crescent  nuclei.  A  further  stage  is  rep- 
resented in  villi  whose  mesodermal  stroma  contains  but  few 
trophoblast  nuclei  and  where  the  syncytium,  thin  as  endothelium, 
rests  on  no  layer  of  Langhans  (Fig.  34).  In  numerous  villi,  at 
one  end  is  found  the  typical  structure  of  a  complete  villus,  the 

<?l e  r  ~ ,  j  > 

.'<  o°  '  -"-"'  ■•'* 

,:'-        •'  ■'    .  ",      -> 

%*#  i  -   ■•/•'■    ^ -oi  ■•:■■■ 


v ■"■<aT.i».u'   a  r? 

mimhkc. 


Fig.  33. — Villus  with  beginning  centre  of  mesoderm.     The  syncytial  covering 
contains  vacuoles  and  crescent-shaped  nuclei. 


syncytial  covering  evidencing  sprouts  of  a  polynuclear  char- 
acter (Fig.  35).  The  other  end  of  the  villus  is  of  a  younger 
stage.  The  syncytium  is  there  at  the  period  characterized  by  the 
frothy,  finely  granular  character  of  the  protoplasm,  while  the 
nuclei  are  irregular  in  form  and  do  not  stain  deeply  (Fig.  35). 
Here,  too,  the  change  of  trophoblast  nuclei  into  syncytial  ele- 


Fig.  34. — Older  villus  with  thin  syncytium  and  no  layer  of  Langhans. 

ments  is  evident.  In  the  cell  groups  (Fig.  35a)  we  observe  a  cov- 
ering of  syncytium  which  at  numerous  points  extends  into  the 
substance  of  the  cell  group,  forming  protoplasmatic  masses  of  a 
thin  endothelial  character  or  of  a  polynuclear  nature,  and  which 
divide  the  cell  groups  into  irregular  fields  (Fig.  35&)  wherein 
may  be  recognized  the  various  early  stages  of  subsequent  villi 
(Fig.  35c) .     This  invasion  of  syncytial  cells  is  not  alone  an  active 


72  THE  CHORIONIC  VILLI. 

growth,  but  is  due  to  the  infiltration  of  a  cell  group  by  blood, 
which  transforms  the  cells  with  which  it  comes  into  contact  into 
syncytium.     Here  most   distinctly   can  the   gradual   transition 


Newly  formed 
syncytium. 


Older  syncytial 
covering. 
Syncytial 

sprouts.  £ 


Fig.  35. — Villus  showing  an  older  stage  in  the  left  half  and  a  younger  stage 
in  the  right  half. 


W^s?? 


r 


V 

Fig.  35a. — Cell  group  with  syncytial  elements  invading  it  at  various  points. 

from  trophoblast  to  syncytium  be  observed.  The  large,  poly- 
nuclear  groups  and  knobs  of  syncytium,  the  so-called  giant  cells, 
are  found  at  all  points  in  the  intervillous  space.     The  nuclei 


THE  CHORIONIC  VILLI. 


73 


^S'r*^  -----  -    V-v        A*       %  . 


^?' 


V 


Fig.  356. — Further  stage  of  Fig.   35a.     Cell   group  divided   by  syncytial   ele- 
ments, with  the  formation  of  fields  which  represent  future  villi. 


Zi    4„, 


d  '  t     * 


j 


IV. 


''/', 


r^** 


Xftf* 


T.  8. 


»>°5' 


Fig.  35c. — A  further  stage  of  Fig.  356.  Cell  group  divided  into  syncytial 
masses  and  villi.  V2,  villus  in  whose  stroma  are  nucleated  red  blood  cells ; 
8j  a  syncytial  mass  ;  T,  syncytial  nuclei  resulting  from  changes  in  the  tropho- 
blast  cells ;  Tr.,  trophoblast  cells  with  beginning  change  to  syncytial  nuclei ; 
Vv  villus  with  whose  syncytial  covering  numerous  bridges  of  syncytium  are 
connected. 


74  THE  CHORIONIC  VILLI. 

are  round,  flat,  and  crescent  shape.  They  are  very  frequently 
attached  to  the  villi  by  larger  or  thinner  pedicles.  They  are  fre- 
quently found  at  the  tips  of  the  villi,  where  they  represent  the 
change  of  the  small  so-called  cell  groups,  or  pillars,  to  syncytium. 
The  villi  are,  then,  in  their  various  stages  simply  reproductions 
of  what  is  found  in  the  membrana  chorii. 


CHAPTER  IX. 
THE    MEMBRANA    CHORII. 

The  great  growth  of  the  ectodermal  cover  in  the  ova  of  ani- 
mals has  been  made  known  to  us  by  Van  Beneden,  Duval,  Nolf, 
and  especially  by  Hubrecht,  who  gave  it  the  name  trophoblast. 

In  1889  Hubrecht,  in  examining  the  placenta  of  the  hedge- 
hog, found  a  decided  resemblance  in  numerous  points  to  the 
human  placenta.  He  asked  then  that  the  following  questions 
with  regard  to  the  human  ova  should  be  studied : 

1.  Can,  in  the  earliest  stages  of  human  ova,  evidences  be  found 
of  a  trophospherical  tissue  between  the  villous  covered  ovum 
and  the  inner  surface  of  the  decidua  reflexa? 

2.  Are  there  in  this  tissue  blood  vessels  which  receive  their 
supply  from  those  blood  vessels  which  run  in  the  reflexa? 

3.  Can  evidences  of  a  trophospherical  tissue  be  found  in  the 
serotinal  region? 

The  discussion  of  the  histology  of  gestation  in  both  uterus  and 
tube  shows  that  the  various  processes  in  the  development  of  the 
human  placenta  resemble  these  observed  in  animal  placentation. 

It  must  be  noted  that  these  processes  follow  the  steps  observed 
by  Hubrecht,  Maximow,  Opitz,  etc.  Yet  there  are  still  many  di- 
verging views  as  to  the  origin  of  the  syncytial  covering  of  the 
villi,  as  has  been  also  observed  in  this  regard  in  the  investigations 
in  animals. 

Selenka  and  Strahl,  in  their  examination  of  young  human  ova, 
find  their  views,  gained  in  the  examination  of  animal  placentas, 
sustained— namely,  that  the  syncytial  layer  originates  from  the 
uterine  epithelium.  "With  this  view  Kossmann  and  Merttens 
agree.  Eckardt  finds  that  the  syncytium  originates  from  the 
maternal  endothelium.  Spee  states  that  the  syncytium  develops 
from  the  connective-tissue  cells  of  the  decidua.  Langhans  con- 
siders the  syncytial  layer  ectodermal,  and  the  inner  layer  of 
Langhans  mesodermal.  Leopold  and  Gaisser  consider  the  layer  of 
Langhans  to  be  of  mesodermal  origin  because  they  find  these  cells 
in  the  mesoderm  of  the  villi.  Frankel  is  uncertain  as  to  the  ori- 
gin of  the  syncytium  in  human  ova,  and  finds  transitions  between 


76  THE  MEMBRANA  CHORII. 

the  cell  of  Langhans  and  cells  situated  in  the  mesoderm  of  the 
villi.  Kastschenko,  Minot,  Van  Heukelom,  and  Ulesko-Stroga- 
nowa  consider  both  layers  to  be  of  fetal  origin. 

Eckardt,  who  holds  that  the  syncytium  originates  from  the 
maternal  endothelium  ( ? ) ,  states  that  the  capillaries  of  the  de- 
cidua  which  form  lacunas  under  the  surface  have  a  varying  char- 
acter. Many  possess  a  distinct  growth  of  the  wall  elements, 
which  is  often  so  great  that  he  would  consider  these  areas  to  be 
sections  of  glands,  were  it  not  for  the  blood  therein  contained. 
We  knoAV  that,  in  the  decidua  menstrualis  and  graviditatis,  blood 
may  enter  the  glands  between  the  epithelial  cells  or  may  break 
into  the  glands.  The  epithelium,  which,  especially  in  the  neigh- 
borhood of  the  ovum,  grows  distinctly  and  shows  an  enlarged 
elongated  protoplasm,  resembles  to  a  certain  degree  the  syncytium. 
These  cells,  however,  degenerate  through  the  action  of  the  blood 
and  the  glands  are  destroyed  or  pushed  aside.  From  his  de- 
scription it  is  quite  evident  that  Eckardt  was  describing  such 
areas,  which  he  mistook  for  a  growth  of  maternal  endothelium. 
With  these  remarks  the  views  of  Eckardt  may  be  dismissed. 

Merttens  found  in  the  particles  obtained  by  curetting  sixteen 
days  after  the  last  menstruation  a  few  sections  of  an  ovum  with 
the  enveloping  decidua.  He  describes  (1)  the  chorion  and  the 
villi.  On  the  latter  are  cell  groups,  and  between  them  are  found 
spaces  constituting  the  intervillous  space.  (2)  The  spongiosa, 
containing  numerous  glands,  and  (3)  the  compacta,  a  pale  zone 
lying  between  1  and  2  and  containing  large  pale  cells,  between 
which  are  numerous  darkly  stained  nuclei. 

In  the  compacta  he  finds  large  cells  and  large  spaces.  Between 
the  large  cells  syncytial  masses  are  irregularly  distributed.  The 
cell  spaces  are  round,  long,  or  irregular,  and  often  empty  into 
the  intervillous  space.  They  contain  blood  and  are  lined  with 
syncytial  masses,  which  at  some  points  are  very  thin  and  at  other 
points  quite  thick.  Where  these  spaces  empty  into  the  intervil- 
lous space  the  syncytial  masses  continue  into  the  syncytium  of 
the  villi.  Merttens  does  not  know  whether  these  spaces  are 
glands,  vessels,  or  lymph  spaces.  They  are  possibly,  however,  the 
lacunae  of  Hubrecht,  Peters,  and  Opitz. 

The  epithelia  of  the  glands  are  like  beaker  cells,  and  on  their 
free  tips  is  a  half-moon  of  glycogen.  The  glands  show  pa- 
pillary projections  (compare  Fig.  145).  Merttens  believes  that 
the  syncytium  results  through  a  change  of  the  surface  and  gland 
epithelium  ( ?).     In  his  Fig.  8  Merttens.  represents,  in  the  upper 


THE  MEMBRANA  CHORII.  I  I 

portion,  the  epithelium  of  such  a  gland,  and  the  lower  half 
represents  syncytial  masses.  He  believes  that  the  latter  result 
from  these  epithelial  cells,  which  lose  their  cylindrical  form  and 
unite.  From  his  descriptions  and  his  drawings  it  is  neither 
clear  nor  probable  that  the  epithelium  changes  into  final  syn- 
cytial masses.  Besides,  this  area  is  taken  from  decidua  parti- 
cles not  connected  with  the  ovum,  and  at  no  point  can  he  find  the 
epithelium  of  the  glands  contributing  in  any  tvay  to  the  syncy- 
tium of  th.e  chorion. 

On  the  contrary,  this  ovum  is  at  the  stage  where  the  trophoblast 
is  almost  consumed  by  the  growth  of  the  intervillous  space, 
and  the  cell  groups  at  the  end  of  the  villi,  which  Merttens  calls 
points  of  union  between  the  villi  and  the  decidua,  are  really  the 
remains  of  the  trophoblast. 

In  a  very  early  ovum  described  by  Spee  the  villi  are  covered 
with  two  layers.  The  inner,  the  cell  layer  of  Langhans,  he  at- 
tributes to  the  ectoderm.  The  outer  layer,  the  syncytium  or 
adventitia  of  the  ovum,  he  describes  as  follows :  ' ' This  layer  is 
often  lifted  off  from  the  chorion  ectoderm.  It  appears  as  a 
continuous  thin  streak  of  protoplasm  with  more  or  less  closely 
grouped  nuclei  arranged  in  a  single  row.  In  the  layers  of  the 
enveloping  zone  lying  near  the  ovum  are  found  cells  which, 
through  a  diffuse  staining  of  the  nucleus  and  through  the  vacu- 
olar character  of  the  protoplasm,  resemble  the  cell  elements  of 
the  syncytium  very  much.  In  the  space  between  the  serotina 
and  the  ovum  (intervillous  space)  we  find  them  often  close  to- 
gether and  not  distinctly  separated,  so  that  here  the  early  stages 
of  the  polynuclear  protoplasmatic  groups  are  present.  Suclt 
groups  are  also  found  united  to  the  membrana  chorii.  Concern- 
ing their  origin  opinions  differ.  I  have  never  observed  a  mitosis 
or  an  amitosis  in  their  nuclei.  The  idea  that  the  chorion  ecto- 
derm furnishes  these  masses  may  be  set  aside  because  of  the  sharp 
division  between  these  two  layers  by  a  cuticula.  These  condi- 
tions prove  that  the  syncytial  formation  does  not  increase  through 
a  division  of  the  nucleus  or  the  cell  in  the  intervillous  space. 
Since,  however,  an  increase  in  the  amount  of  the  syncytial  sub- 
stance occurs  within  the  intervillous  space,  this  can  only  be 
explained  through  a  ivandering  of  already  finished  masses  from 
the  connective  tissue  of  the  compacta  into  the  ovum.1  Epithelial 
cells  cannot  be  considered  as  the  source,  since  the  maternal 
cavity  surrounding  the  ovum,  even  in  the  earliest  stages,  shows 

^ymplasma. 


(O  THE  MEMBRANA  CHORII. 

no  epithelial  lining,  although  in  the  later  stages  closely  pressed 
glands  are  present  all  about  the  ovum  and  their  epithelium  is 
preserved  at  least  up  to  the  end  of  the  first  month."  It  may 
be  seen  that  Spee  left  out  of  consideration  any  possible  action  of 
the  blood  upon  the  ectoderm  cells  as  an  aid  to  the  formation  of 
syncytium.  His  decidua  cells,  resembling  syncytium,  are  pos- 
sibly changed  trophoblast  cells1.  Cells  from  without  probably 
form  the  syncytial  covering  of  the  villi  and  of  the  membrana 
chorii,  in  his  opinion.     We  think  they  are  trophoblast  cells  of 


m, 


to  op 

5(0   ; 


o  © 
SO 


-.'.-%_ 


'■>. 


ll     ii 


*-.*: 


- 


2  P 
5  ca 


;««  -f»  &«  »S  SS° 

f^°  i^o  soo  fe;v  OO 

Pig.   36. — Transverse  section  through  the  fetal   sac  or   membrana  chorii   of  a 

four-  to  five-weeks  ovum. 

fetal  ectodermal  origin,   acted  on  by  the  blood — a  possibility 
which  he  left  out  of  consideration. 

Fig.  36  represents  a  transverse  section  through  the  greatest 
diameter  of  the  ovum  loosely  connected  with  the  decidua  in 
the  fourth  or  fifth  week  of  uterine  gestation.  The  centre  is  a 
space  lined  with  a  double  parallel  layer  of  cells  arranged  in 
single  file.  This  also  loses  its  parallel  arrangement  at  certain 
points,  where  cells  of  the  same  character  are  found  in  groups 
several  layers  deep. 

irThe  resemblance  of  changed  decidua  cells  to  the  future  syncytium  is 
often  striking.     See  foot  note,  p.  87. 


THE  MEMBKANA  CH0R1I.  79 

External  to  these  cells,  in  the  entire  circumference  of  the  sac, 
is  a  substance  staining  a  deeper  red  and  composed  of  extremely 
fine,  granular,  and  thin-fibred,  cotton-like  material.  In  it,  at 
numerous  points,  are  isolated  and  grouped  cells  which  look  like 
nucleated  red  blood  cells. 

The  next  stratum  is  formed  of  round  and  oval  cells,  of  the 
same  character  as  the  lining  of  the  central  space,  but  arranged  in 
several  somewhat  parallel  layers.  Between  these  cells  is  a  fine 
fibre-like  substance,  like  the  one  just  described,  but  taking  a 
lighter  red  stain.  The  outer  cells  are  rounder  and  more  spher- 
ical than  the  inner,  and  the  outermost  cells,  with  a  clear  proto- 
plasm and  distinct  nucleus,  form  a  single  layer  of  distinct  cells 
with  distinct  cell  boundaries  (36). 

The  extreme  external  covering  of  the  membrana  chorii  is  of  a 


-'-©»    ■  ^?*tv  ■           s         ft 

m  >  \  f 

■x- ■•'**■  i%  -^  7 
■f -1 


Vacuoles 


t    '■■£-£ ■  ■'.  'v.  '  Trophoblast 

r  -'    *  cells 


Fig.  37. — Vacuoles  representing  body  of  trophoblast  cells,  while  the  nucleus  is 
a  crescent  in  the  circumference.     From  the  membrana  chorii  of  Fig.  36. 

plasmodial  character,  and  contains,  nuclei  of  various  forms  and 
evidences  many  vacuoles  (Fig.  37).  Each  vacuole  represents 
the  space  filled  by  a  trophoblast  cell,  the  nucleus  being  com- 
pressed at  one  point  into  a  small  crescent.  At  certain  points 
outgrowths  are  present  which  contain  larger  and  smaller  areas 
of  granular  and  plasmodial  character,  the  aforementioned  dis- 
tinct cells,  blood,  and  protoplasmatic  groups  containing  small 
pale  cells,  small  dark  nuclei,  and  nuclei  undergoing  degenera- 
tion. Attached  to  the  membrana  chorii  and  all  about  it  are  in- 
numerable villi  in  all  stages  of  growth,  young  and  old.  The 
older  villi  present  the  same  structure  and  possess  the  same 
cells,  including  the  nucleated  red  blood  cells,  as  are  found  in  the 
chorionic  membrane. 

The  conclusion  gained  from  a  comparison  of  this  specimen 
with  the  structure  of  the  villi  is  the  following:     The  single 


80  THE  MEMBRANA  CHORII. 

layer  of  cells  immediately  under  the  plasmodium  of  the  cho- 
rionic membrane,  the  spheroidal  cells  under  it,  the  distinct  cells 
found  in  the  outgrowths,  the  spheroidal  cells  in  the  young  villi 
and  in  the,  cell  groups  which  form  the  new  villi,  and  the  cell 
layer  of  Langhans,  are  identical  and  represent  the  ectodermal 
trophoblast  cells.  The  villi  are  simply  excrescences  of  the  mem- 
brana  chorii. 

When  the  blood  comes  in  contact  with  the  trophoblast  cells  it 
does  not  coagulate.  It  does,  however,  exert  a  decided  influence 
on  the  nuclei.  Strahl  found,  in  examining  the  placenta  of 
Galago,  that  the  blood  extravasated  from  the  vessels  of  the 
uterus  is  made  use  of  by  the  fetus,  in  that  the  degenerating 
products  of  the  extravasated  blood  cells  are  taken  up  and  ab- 
sorbed. These  products  are  found  in  the  form  of  larger  and 
smaller  yellow  granules  in  the  gland  epithelium,  which  the  latter 
uses  in  furnishing  an  iron-containing  gland  secretion.  In  the 
placenta  of  other  animals  the  blood  extravasated  from  the  ves- 
sels of  the  uterus  is,  taken  up  and  absorbed  by  the  ectoderm 
cells,  and  in  certain  animals  the  fetus  obtains  its  nutrition  be- 
cause the  ectoderm,  covering  the  villus,  takes  up  the  substance 
given  off  by  the  uterine  epithelium.  Merttens  observes  that 
Lieberkiihn  in  the  placenta  of  the  dog,  and  Strahl  in  the  pla- 
centa of  the  mole,  find  ectoderm  cells  taking  up  and  absorbing  red 
blood  cells.  Peters  states  that  Tafani,  in  the  placenta  of  the 
cat,  found  chorion  ectoderm  cells  outside  of  the  placenta  taking 
up  red  blood  cells.  We  find  much  blood — that  is,  red  blood 
cells— in  the  syncytium.  It  is  also  found  in  the  vacuoles.  Peters 
believes  that  the  blood  takes  part  in  the  changes  of  the  tropho- 
blast nuclei  and  that  its  elements  contribute  to  the  formation 
of  the  protoplasmatic  masses  known  as  the  syncytium.  "Not 
only  the  blood  plasma,  but  also  the  nuclei  of  red  and  white 
blood  cells,  pass  into  the  composition  of  these  masses."  It  may 
be  seen  in  Fig.  315  that  the  red  blood  cells  change  into  a  detritus 
and  combine,  so  that  finally  small  irregular  areas  containing  small 
nuclear  remnants  result.  A  gradual  destruction  of  red  blood 
cells  takes  place,  and  the  presence  of  leucocyte  nuclei  may  be 
observed.  The  plasma,  when  acting  suddenly  and  in  large 
amounts,  causes  the  trophoblast  nuclei  to  shrink  and  take  on  a 
dark  stain.  When  acting  slowly  it  disintegrates  them,  flattens 
them,  so  that  in  a  resulting  homogeneous  protoplasm  nuclei  of  all 
forms  may  be  found.  It  is  evident,  then,  that  the  protoplasm 
of  the  syncytium  is  the  product  of  the  blood  cells,  the  blood 


THE  MEMBRANA  CHORII.  81 

plasma,  and  the  protoplasm  of  the  trophoblast  cells.    The  nuclei 
of  the  syncytium  are  the  changed  trophoblast  nuclei. 

Wherever  blood  comes  in  contact  with  fetal  cells  syncytium 
results,  whether  in  the  decidua  or  in  the  intervillous  space,  so 
that  syncytium  really  plays  the  part  of  an  endothelium  and  at 
all  periods,  especially  in  the  later  stages,  resembles  endothelium 
so  closely  that  it  was  naturally  mistaken  for  it  in  nearly  all  the 
earlier  investigations. 

Many  observers  have  noted  a  brush-like  covering  on  the  syn- 
cytium, though  I  have  never  found  it.  This  striated  surface  on 
the  syncytial  covering  of  the  chorion,  and  often  observed  on  the 
isolated  polynuclear  protoplasmatic  masses,  appears  to  Spee  to 
be  a  sort  of  fibrillation  on  the  cell  protoplasm.  He  believes 
that  it  originates  through  the  influence  of  a  sap  current  toward 
the  ovum,  because  such  a  brush-like  fibrillation  is  found  in  those 
places  where  a  regulated  transit  of  products  through  cells  oc- 
curs, as  in  parts  of  the  excretory  ducts  of  the  salivary  glands 
and  the  kidneys  on  the  side  toward  the  connective  tissue,  and 
also  perhaps  in  the  osteoblasts  in  the  Howship  lacuna?  of  bone. 
6 


CHAPTER  X. 

THE  BLOOD-FORMING  FUNCTION  OF  THE 
TROPHOBLAST. 

In  another  particular,  as  I  believe  can  be  shown,  the'  resem- 
blance between  the  processes  of  development  in  the  human  being; 
and  those  in  animals  is  carried  out  still  further — namely,  the 
formation  of  blood  by  the  fetal  placenta. 

In  sections  through  the  umbilical  vesicle  of  Tarsius  and  Tu- 
paja,  Hubrecht  finds,  polynuclear  cells  which  he  considers  to 
be  mother  blood  cells.  Their  nuclei  result  through  fragmen- 
tation of  a  large  nucleus.  The  individual  nuclei  within  the 
mother  cell  then  become  surrounded  with  a  special  circle  of 
plasma.  When  the  original  mantle  of  the  protoplasm  of  the 
large  cell  is  lost,  the  included  cells  are  freed,  forming  embryonal 
nucleated  red  blood  cells.  During  their  circulation  in  the  em- 
bryonal fetus  the  nuclear  membrane  disappears  and  the  nucleus 
changes  to  a  drop  in  which  the  chromatin  diminishes,  while  the 
protoplasm  begins  to  resemble  the  former  nucleus.  The  cells 
become  gradually  smaller,  and  the  final  forms  do  not  result 
from  the  protoplasm  but  from  the  nuclei  of  the  cells.  The 
blood  cells  originate,  then,  from  the  original  nucleus  of  a  mother 
blood  cell.  Hubrecht  finds  the  same  steps  in  the  placenta  of 
Tarsius  as  in  the  umbilical  vesicle.  He  finds  the  same  to  occur 
in  the  trophoblast  and  in  the  maternal  spongia,  and  even  in  the 
vessels  which  lie  between  the  glands.  In  the  placenta  of  Tupaja 
the  same  steps  are  noted,  but,  in  addition,  the  epithelium,  as  well 
as  the  connective  tissue  of  the  decidua,  is  the  seat  of  red  blood 
cells  derived  from  nuclei. 

In  his  ovum  v.H.  Spee  describes  the  mesoderm  layer  as  follows : 
He  finds  two  different  cell  forms  occurring  side  by  side  and  inter- 
mingled :  (1)  Branched  cells,  extending  into  fine  threads  which 
project  in  all  directions  and  which  may  well  be  considered  con- 
nective-tissue fibres.  Where  these  cells  occur  singly — for  in- 
stance, at  certain  points  in  the  abdominal  pedicle  and  in  the 
villi— the  mesoblast  appears  exceedingly  poor  in  nuclei.  Strong- 
ly-stained specimens  are  necessary  to  see  the  numerous  fine, 


BLOOD-FORMING  FUNCTION  OF  THE  TROPHOBLAST.  83 

wavy,  and  sharply  contoured  fibres  of  the  embryonal  connective 
tissue.  (2)  Between  these  structures  are  found  larger,  strongly 
prominent  spindle  cells  with  oval  nuclei,  arranged  sometimes 
closely  together  like  bundles,  and  at  other  points  separated 
from  each  other  by  wide  spaces  without  evident  contents. 
The  course  of  these  fibres  follows,  with  noticeable  constancy,  the 
curves  of  the  free  mesoderm  surface — that  is,  the  surface  covered 
with  epithelium. 

In  our  opinion  many  of  the  second  form  of  cells  are  possibly 
ectodermal.  In  an  ovum  described  by  Reichert,  on  the  inner 
side  of  the  chorion  is  a  substance  which  he  considers  to  be  a 
mucoid-like  deposit  and  which  also  extends  into  the  villi.  The 
cavity  of  the  ovum  is  likewise  filled  with  this  substance.  Spee 
considers  this  to  be  mesoderm  tissue,  although  Reichert  de- 
scribes the  contents  of  the  ovum  simply  as  a  mucoid  substance 
without  cells:  Spee  says  that  the  contents  of  the  amnion  and 
of  the  umbilical  vesicle  of  ova  hardened  in  alcohol  never  coagu- 
late, but  such  a  condition  does  take  place  in  the  wide  mesoderm 
slit  of  dead  young  human  ova. 

Thus  the  early  embryonal  mesoderm  tissue  of  the  membrana 
chorii  and  of  the  villi  is  very  poor  in  cells,  and  the  description  of 
Reichert,  characterized  by  Spee  as  mesoderm  substance,  selves 
to  characterize  as  mesoderm  the  non-celled  material  found  be- 
tween the  central  space  and  the  external  layers  of  cells  seen  in 
Fig.  36  and  also  found  in  many  of  the  younger  villi. 

It  has  been  mentioned  that  Langhans  considers  the  cell  layer  to 
•be  of  mesodermal  origin,  and  that  Leopold  holds  the  same  view 
because  he  finds  transitions  between  the  stroma  cells  and  the 
cell  layer.  Frankel,  who  believes  that  the  cell  layer  and  the 
syncytium  are  probably  identical,  finds  the  question  difficult  of 
solution  because  of  the  numerous  villi  whose  interior  is  com- 
posed of  ectodermal  trophoblast  cells.  We  have  called  atten- 
tion to  this  occurrence  as  a  frequent  one,  and  have  likewise  ob- 
served the  resemblance  between  the  cell  layer  of  the  membrana 
chorii  and  the  several  layers  of  cells  under  it  which  are  embedded, 
however,  in  mesoderm  substance  (Fig.  36).  The  origin  of  the 
villi,  the  fact  that  they  are  formed  out  of  solid  trophoblast 
groups,  the  fact  that  only  later  does  mesodermal  tissue  reduce 
them  to  the  generally  single  layer  of  Langhans,  the  fact  that  in 
this  reduction  to  a  single  layer  many  trophoblast  cells  are  left 
embedded  in  the  stroma  of  the  villi  and  the  membrana  chorii, 
and  the  numerous  transitions  between  these  cells  and  the  cells  of 


84  BLOOD-FORMING  FUNCTION  OF  THE  TROPHOBLAST. 

Langhans,  prove  that  they  are  ectodermal  cells  situated  in  a  basis 
of  mesoderm  substance  in  which  only  later  mesoderm  nuclei 
appear. 

As  the  villi  grow  older,  these  ectoderm  cells  are  crowded  by 
the  growing  mesoderm  tissue,  so  that  some  degenerate,  while 
others  take  part  in  the  following  important  changes — that  is, 

THEY  FORM  RED  BLOOD  CELLS. 

In  the  same  manner  that  the  external  trophoblast  cells,,  which 
come  in  contact  with  the  blood,  obtain  from  it  a  protoplasmatic 
envelope,  while  they  themselves  form  the  nuclei,  in  quite  the 
same  manner  these  cells  situated  in  mesoderm  are  seen  to  gradu- 
ally change  their  form,  become  darker,  become  surrounded  by  a 
red-staining  granular  protoplasm  of  the  same  character  as  the 
mesodermal  tissue.  They  then  represent  nucleated  red  blood 
cells.  They  are  often  seen  in  stages  where  the  nucleus  becomes 
fragmented  or  divided  into  other  cells.  These  larger  and  smaller 
nucleated  reds  are  found  isolated  or  in  groups,  often  lying  in 
spaces  or  slits  of  the  mesoderm  of  the  villi  and  membrana  chorii. 
These  spaces  are  often  surrounded  by  very  long,  very  dark,  and 
spindle-like  cells,  evidently  forming  the  endothelium  of  the  fu- 
ture capillaries. 

M1  e  have  observed  the  statement  that  in  animals  the  mesoderm, 
which  enters  the  trophoblast  groups  and  forms  the  stroma  of  the 
villi,  carries  with  it  the  branches  of  the  allantoic  vessels.  Ves- 
sels, however,  are  not  present  in  the  villi  of  the  human  ovum 
until  the  third  week,  and  the  villi  are  then  filled  with  mesoderm 
or  ectoderm  cells,  and  it  would  be  impossible  for  extensions  of 
the  allantoic  vessels  to  enter  into  the  innumerable  extensions  of 
the  membrana  chorii  constituting  the  villi.  The  process  followed, 
however,  is  probably  the  following : 

Mesoderm  does  not  enter  as  a  distinct  tissue  into  the  tropho- 
blast elements  after  they  have  been  reduced  by  the  maternal 
blood  to  syncytium,  but  is  present  between  the  trophoblast  cells 
from  the  very  earliest  period,  as  may  be  seen  in  the  description 
of  a  tubal  ovum.  When,  therefore,  a  trophoblast  cell  group 
comes  in  contact  with  maternal  blood,  the  outer  cells  are  changed 
to  syncytium,  underneath  which  results  the  cell  layer  of  Lang- 
hans, which  in  the  still  later  periods  disappears.  The  mesoderm 
substance,  when  increasing  in  amount,  dilates,  the  villus  and 
forms  the  stroma.  In  the  resulting  stroma  are  left  the  remain- 
ing more  or  less  scattered  trophoblast  cells.  From  these,  nu- 
cleated red  blood  cells  are  formed,  which  lie  in  small  slits  or 


BLOOD-FORMING  FUNCTION  OF  THE  TROP1IOBLAST. 


85 


spaces,  which  spaces  become  lined  with  endothelium,  thus  form- 
ing capillaries.  These  capillaries  gradually  increase  and  finally 
become  very  numerous,  having  a  tendency  to  lie  close  under  the 
epithelial  covering  of  the  villi.  "Whether  any  of  these  tropho- 
blast  cells  take  part  in  the  formation  of  the  endothelium,  it  is 
impossible  to  say  with  certainty.  These  same  processes  are  ob- 
served in  the  membrana  chorii.  These  capillaries  in  the  villi  and 
in  the  membrana  chorii  later  unite  with  the  umbilical  vessels 
which  make  their  way  through  the  abdominal  pedicle. 


Abdominal  pedicle 


/A 


Sinuses  containing  nucleated  red 
blood  cells 


Syncyt.  outer 
covering 
of  sac 
Vessels  in 
urn  bilical 
cord 


Central  cavity  of  fetal  sac 


Fig.   38. — Membrana   chorii   of  tubal   ovum. 

The  nucleated  red  blood  cells,  in  their  subsequent  circulation 
through  the  fetus,  become  changed,  and  from  the  third  month 
on  ordinary  red  blood  cells  are  found.  In  the  membrana  chorii 
of  our  uterine  ovum  the  same  stages  of  capillary  development 
may  be  observed,  but  to  a  less  extent  than  in  some  of  the  villi 
which  already  possess  numerous,  and  distinct  capillaries.  In  the 
later  stages  this  process  is  more  marked  in  the  membrana  chorii 
than  in  the  villi,  as  may  be  seen  from  the  following  description 
of  a  tubal  gestation  with  well-preserved  fetus  i1 

JThe  possibility  that  these  nucleated  red  blood  cells  came  from  the 
fetus  was  not  left  out  of  consideration. 


86  BLOOD-FORMING  FUNCTION  OF  THE  TROPHOBLAST. 

The  fetus  was  lying  in  the  central  cavity  of  the  ovum  (Fig.  38) 
attached  by  an  umbilical  pedicle  which  entered  the  placenta  at 
the  site  to  be  mentioned  later.  The  fetus  was  one  centimetre 
long;  the  abdominal  wall  was  not  yet  closed,  and  the  arm  and 
leg  formations  were  just  evident  as  small  pinhead  knobs.  The 
cavity  of  the  ovum  is  lined  by  a  membrane  composed  of  flat- 
tened cells  with  distinct  nuclei.  At  various  points  in  the  cir- 
cumference of  the  membrana  chorii,  and  especially  at  the  point 
where  the  abdominal  pedicle  is  attached,  are  numerous  larger 
or  smaller  spaces,  separated,  sometimes,  from  the  maternal  blood 
by  only  a  single  or  double  layer  of  cells,  which  at  many  points 
are  of  a  distinctly  plasmodial  character.  The  membrana  chorii 
has  at  various  points,  and  especially  at  the  placental  site,  numer- 
ous villi  attached  to  it  and  numerous  small  projections  of  the 
same  structure  as  villi.  These  spaces,  or  sinuses,  contain  masses 
of  round,  red-staining  protoplasmatic  masses  with  dark  cen- 
tral nuclei,  many  of  which  are  undergoing  division— nucleated 
red  blood  cells.  It  seems  possible  that  many  of  these  sinuses  or 
spaces  represent  dilatations  of  the  parallel  row  of  cells  observed 
in  Fig.  36,  wherein  were  noted,  at  various  points,  groups  of  cells 
of  a  trophoblast  character.  It  is  probable  that  those  groups 
too  form  the  nucleated  red  blood  cells  observed  in  these  sinuses. 

The  largest  of  these  sinuses  are  present  near  the  insertion  of 
the  abdominal  pedicle,  and  all  of  them  are  separated  from  the 
maternal  blood  of  the  intervillous  space,  often  by  only  a  single 
layer.  These  sinuses  may  represent,  then,  areas  in  the  membrana 
chorii  filled  with  nucleated  red  blood  cells  of  placental  tropho- 
blast origin,  which  subsequently  enter  the  fetal  circulation. 

In  the  pedicle  itself  a  change  to  the  subsequent  non-nucleated 
red  blood  cells  may  be  observed,  for  in  its  substance  are  fetal  ves- 
sels and  sinuses  filled  with  cells  of  a  different  character.  They 
are  small,  with  a  thin  circumference  of  protoplasm  and  a  dark 
nucleus  filling  out  almost  the  entire  cell  body.  These  represent, 
then,  the  later  stages  of  the  red  blood  cells. 

The  resemblance  of  this  process  to  the  one  noted  by  Hubrecht 
in  Tupaja  and  Tarsius  carries  out  still  further  the  resemblance 
of  the  various  processes  in  the  human  placenta  to  those  in  the 
placentas  of  animals.  That  this  theory  and  explanation,  whereby 
red  blood  cells  are  formed  of  trophoblast  ectodermal  cells,  is  a 
rational  one  and  proven  by  the  examination  of  our  specimens 
seems  to  me  evident.  In  addition,  it  serves  to  explain  the  pres- 
ence of  trophoblast  cells  in  the  interior  of  the  villi — a  fact  which 


BLOOD-FORMING  FUNCTION  OF  THE  TEOPHOBLAST.  87 

has  led  many,  who  have  considered  them  mesodermal  because 
situated  in  the  mesodermal  stroma,  to  likewise  call  the  cells  of 
Langhans  mesodermal.  The  formation  of  nucleated  red  blood 
cells  from  trophoblast  cells,  on  the  addition  of  a  protoplasm  of 
mesodermal  origin,  would  serve  to  make  their  resemblance  to  syn- 
cytium very  great;  for  the  latter  is  composed  of  trophoblast 
nuclei  with  a  protoplasm  largely  composed  of  maternal  blood 
plasma.  If,  as  many  sections  have  suggested,  the  capillaries  were 
lined  by  endothelium  which  is  also  formed  of  these  trophoblast 
nuclei,  the  resemblance  of  this  process  to  the  formation  of  syn- 
cytium would  be  further  increased;  for  the  syncytium  simply 
plays  the  part  of  endothelium,  separating  the  other  fetal  cells 
at  all  times  from  the  circulating  blood. 

Uterine  (as  well  as  tubal)  ova  furnish  us  with  the  following 
positive  conclusions: 

1.  The  human  ovum  possesses  an  ectodermal  growth  of  cells, 
the  trophoblast,  consisting  of  closely-grouped  cells. 

2.  When  vascularized  by  maternal  blood,  a  second  external 
layer,  consisting  of  plasmodial  mononuclear  and  polynuclear  ele- 
ments, results. 

3.  Elements  of  the  maternal  blood  circulating  in  the  spaces 
and  lacunas  of  the  trophoblast  contribute  to  the  protoplasm  of 
the  syncytium.  Among  other  elements,  the  secretion  of  the 
uterine  or  tubal  epithelium  may  likewise  contribute  to  the  for- 
mation of  the  syncytial  protoplasm.  At  any  rate,  much  of  the 
protoplasm  (but  none  of  the  nuclei)  is  of  maternal  origin. 

4.  On  the  villi  and  the  membrana  chorii  the  plasmodial  cells 
form  the  outer  syncytial  layer,  ivhile  the  closely-grouped  cells 
beneath  it  furnish  the  single  layer  of  Langhans. 

5.  The  stroma  of  the  chorionic  villi  is  formed  of  mesodermal 
tissue  in  which  are  later  found  capillaries  communicating  with 
the  umbilical  vessels  and  containing  fetal  blood.  Clear  in  almost 
every  detail,  then,  a  trophoblast  formation,  consisting  of  an  inner 
layer  of  separated  cells  and  an  outer  or  plasmodial  layer  such 
as  is  found  in  the  placental  development  of  animals,  is  present 
in  human  placentation. 

Note. — It  is  to  be  noted  that  the  embedding  of  the  guinea-pig's  ovum  re- 
veals symplasmatic  changes  in  the  decidua  which  make  Spee's  theory  of 
the  maternal  origin  of  the  syncytium  very  attractive.  Certain  it  is  that 
the  decidual  cells  undergo  "syncytial  changes."  Were  we  to  go  but  one 
step  further  and  add  to  the  maternal  blood  symplasmatic  decidual 
structures  as  an  external  factor  in  the  production  of  syncytium,  then 


88  BLOOD-FORMING  FUNCTION  OF  THE  TROPHOBLAST. 

the  theory  of  the  exclusively  fetal  trophoblastic  origin  of  this  tissue 
would  fall  to  the  ground.  The  distinction  between  fetal  and  maternal 
cells  is  often  decidedly  difficult,  and  in  that  fact  lies  the  crux  of  the 
problem.  If  the  view  we  have  chosen  be  correct,  it  must  still  be 
granted  that  the  decidua  undergoes  primary  or  secondary  changes  which 
make  its  resemblance  to  real  syncytium  striking.  Though  often  and 
in  many  specimens  led  to  favor  Spee's  view  by  microscopic  appearances, 
yet  our  choice  of  views  (by  no  means  surely  excluding,  in  whole  or  in 
part,  the  views  of  Spee)  seems  well  founded. 

"Structures  not  wisely  called  'syncytial'  may  be  formed  from  va- 
rious forms  of  tissue,  as  uterine  epithelium,  uterine  connective  tissue, 
fetal  ectoblast,  etc.  Therefore,  especially  when  we  consider  the  vari- 
ations in  placental  formation  in  various  species  of  animals,  it  is  not 
correct  to  speak  of  'the  syncytium'  as  if  all  syncytial  formations  were 
alike.  Therefore,  in  the  guinea-pig,  I  did  not  use  this  word,  but  chose 
the  term  'symplasma'  to  designate  those  structures  (developed  from 
connective  tissue)  comparable  to  syncytium"  (v.  Spee).  Van  Beneden 
calls  this  tissue,  developed  from  ectoblast  in  animals,  Plasmodium. 
Plasmodium  is,  then,  in  the  human  ovum  "trophoblast."  We  believe 
"syncytium"  to  be  the  "Plasmodium"  of  animals.  Decidual  and  other 
uterine  cells  undergo  the  so-called  "syncytial  changes."  It  would  be 
advisable  to  call  these  "symplasmatic"  cells.  The  question  then  is: 
Is  syncytium  of  symplasmatic  or  plasmodial  origin?  "We  hold  the  latter 
view. 


CHAPTER  XI. 

THE  FURTHER  DEVELOPMENT  OF  THE  UTERINE 
PLACENTA. 

Just  as  during  the  early  weeks  the  trophoblast  invades  the  tro- 
phospongia  or  decidua,  so  after  the  formation  of  villi  is  the  fur- 
ther course  of  the  ectodermal  trophoolast  and  syncytial  cells  of  a 
destructive  character,  so  far  as  the  decidua  is  concerned.  Fig. 
39  presents  a  fetal  sac  in  situ  in  the  sixth  or  seventh  week  of 


Decid.  vera  y. 


D.  vera,  compressed. 

chorion   laeve 

D.  reflewa  or 

capsularis. 

Decid.  vera  x 


Junction  of  D.  vera, 
serotina  and  reHexa 


Serotinal  area 
Chorion  frondosum 


Decid.  vera. 


Fig.  39. — Uterus  and  fetal  sac  in  situ — 7  weeks — two-thirds  the  size  of  the 
specimen  when  mounted,  and  one-half  the  size  of  the  specimen  before  hardening. 
y,  decidua  vera  with  numerous  glands,  i.e.,  well-marked  spongiosa ;  x,  decidua 
vera  with  compacta  compressed  through  pressure  of  the  sac,  and  evidencing  few 
flattened  glands  in  the  spongiosa. 


uterine  gestation.  The  specimen  from  which  the  drawing  was 
constructed  was  unfortunately  distorted,  yet  the  important  rela- 
tions are  very  clear. 

The  capsularis,  to  which  villi  are  attached,  is  full  of 
darkly-staining  trophoblast  cells,  between  which  and  through 
which  are  blood  spaces  and  blood  extravasations.  Opposite  it, 
but  not  yet  in  contact,  is  the  decidua  vera,  flattened  by  pressure 


90  FURTHER   DEVELOPMENT   OF   THE   UTERINE   PLACENTA. 

of  the  growing  sac,  and  composed  of  pure  decidua  divided  into  a 
superficial  layer,  the  compacta,  and  a  deeper  layer  of  flattened 
glands,  the  spongiosa  (Fig.  40).  Where  the  decidua  vera  is  not 
compressed,  as  at  the  areas  where  decidua  vera,  reflexa,  and 
serotina  join  (Fig.  39),  the  decidua  retains  in  its  deeper  layer  the 
typical  character  of  the  spongiosa,  evidencing  numerous  glands  of 
all  sizes  and  lined  by  preserved  epithelium  of  a  "syncytial"  char- 
acter (Fig.  14&). 


Compacta. 


Glands. 


Muscularis. 


-—■•?:' 


Fig.  40. — High-power  drawing  of  decidua  vera  (compressed)   of  Fig.  39. 


The  decidua  serotina  evidences  in  the  deeper  layers  few  flat- 
tened glands.  The  superficial  layers  are  greatly  changed. 
Where  the  villi  come  in  contact  with  decidua  the  syncytium 
disappears  and  the  cell  groups  enter  the  maternal  tissue  and 
mingle  with  it  (Fig.  41).  This  process  is  carried  on,  then,  by  all 
the  attached  villi  also,  so  that  the  resulting  "decidua"  is  of  the 
same  character  as  the  cell  groups.  This  resulting  tissue  resembles 
the  decidua,  but  its  nuclei  take  a  deeper  stain  and  it  evidences  no 
small-celled  infiltration.     In  it  are  found  cells  composed  of  a 


FURTHER   DEVELOPMENT   OP   THE   UTERINE   PLACENTA. 


91 


structureless  mass  enclosing  one  or  more  cell  nuclei  or  groups  of 
nuclei.     They  resemble  syncytium  and  are  simply  changed  fetal 


Dark  fetal 
cells  invading 
maternc 

tissue. 


w\. 


%\'; 


Fig.  41. — Cell  groups  of  villi  entering  maternal  tissue.     Taken  from  the  sero- 
tinal  or  placental  area  of  Fig.  39. 


Syncytium.    #|j 


Dark  syncytial  J&M/ti*    &  !  SP© 


»& Syncytial  cells. 


,:#*>  i/i-  &..•* 


■£, 


><^ 


«?-^v 


Fig.   42. — Dark  syncytial  cells   infiltrating  decidua  serotina  of  Fig.  39. 


cells.  Without  the  aid  of  these  syncytial  cells,  which  infiltrate 
the  maternal  tissue  very  thoroughly  and  in  all  directions  and 
quite  deeply,  it  is  difficult,  with  the  exception  of  the  darker 


92  FURTHER  DEVELOPMENT   OP   THE   UTERINE   PLACENTA. 

staining,  to  mention  characteristics  which  to  the  beginner  would 
differentiate  fetal  cells  from  the  decidua.  It  is  this  fact  which 
has  made  the  various  questions  depending  on  this  differentiation 
difficult  of  solution. 

The  boundary  between  fetal  and  decidua  cells  shows  degenera- 
tive changes;  the  superficial  glands  are  pushed  aside  and  de- 
stroyed, while  the  deeper  glands  grow,  their  epithelium  swells, 
unites  and  forms  so-called  syncytial  changes.  These  masses  fall 
off  and  finally  degenerate.  The  fetal  cells  at  all  periods  infiltrate 
the  decidua  and  bring  it  to  destruction.  The  advancing  ecto- 
blastic  and  syncytial  cells  have  an  erosive  action  on  the  vessels 
which  prepares  them  and  the  capillaries  for  bursting.  In  this 
way  new  lacunas  and  areas  of  degeneration  result,  and  the  blood 
from  these  open  vessels  changes  the  fetal  cells  to  syncytium  and 
to  villi  and  constantly  increases  the  extent  of  the  intervillous 
space. 

The  cell  groups  of  the  villi  later  diminish  and  disappear.  The 
villi  increase  in  number  and  are  closely  grouped.  Their  stroma 
consists  of  star-shaped  cells,  between  which  are  cells  resembling 
those  of  Langhans.  The  rest  of  the  stroma  is  filled  out  with 
numerous  capillaries,  and  finally  the  syncytium  is  reduced  to  a 
thin  substance  containing  nuclei  (Fig.  44). 


CHAPTER  XII. 
THE    PLACENTA. 

That  part  of  the  decidua  covering  the  embedded  ovum,  plus 
the  scar  of  Reichert,  forms  the  capsularis,  or  decidua  reflexa. 
That  part  of  the  decidua  in  which  the  ovum  is  embedded,  and 
on  which  the  ovum  rests  in  its  early  stages,  is  the  serotina.  Here 
the  main  changes  between  the  ovum  and  villi  on  the  one  hand, 
and  the  decidua  and  maternal  blood  on  the  other  hand,  take  place. 
The  remainder  of  the  decidua  is  the  vera. 

The  villi  in  the  entire  periphery  of  the  ovum  depend  for  their 
growth  and  development  on  connection  with  the  maternal  de- 
cidua and  blood.  At  the  end  of  the  first  month  the  villi  are 
evenly  distributed  over  most  of  the  periphery  of  the  ovum.  With 
the  growth  of  the  ovum  in  the  next  two  months  there  is  a  stretch- 
ing of  the  capsularis,  which,  however,  grows  likewise,  so  that  it 
is  not  much  thinned  except  at  its  summit.  There  is,  however,  in 
these  two  months  a  constantly  slighter  connection  of  the  vessels 
of  the  capsularis  with  the  maternal  vessels  of  the  vera  and 
serotina.  In  addition  the  fetal  vessels  wThich  enter  the  membrana 
chorii  through  the  adherent  band  establish  closer  and  more  im- 
mediate relations  with  the  villi  at  the  serotina,  for  the  abdominal 
pedicle  is  at  this  point. 

As  a  result  we  distinguish  two  divisions  in  the  chorion:  (1)  that 
in  which  new  villi  cease  to  develop  and  in  which  formed  villi 
gradually  degenerate  and  atrophy — the  chorion  Iceve;  and 
(2)  that  in  which  the  villi  increase  hugely  in  number  and  size, 
the  area,  at  the  serotina — the  chorion  f  rondo  sum. 

The  chorion  frondosum  forms  the  placenta.  The  growth  of 
the  uterus  in  the  first  three  months  is  independent  of  the  growth 
of  the  ovum,  and  the  uterus  undergoes  eccentric  development. 
Therefore  the  area  of  the  serotina  increases  in  extent.  The  ovum 
grows  of  its  own  accord,  and  as  a  result  the  area  of  the  chorion 
frondosum  increases  in  extent  and  keeps  pace  with  the  growth 
in  extent  of  the  serotina.  Septa,  of  decidua  extend  between  villi 
and  groups  of  villi,  due  to  the  irregular  invasion  of  the  serotina. 
As  the  ovum  grows  in  the  first  three  months  it  is  covered  by 


94  THE  PLACENTA. 

capsularis  (Fig.  39).  Though  the  capsularis  at  the  end  of  the 
third  month  covers  an  ovum  as  large  as  a  goose  egg,  it  is  fairly 
thick  except  at  its  summit,  and  is  in  contact  with  the  decidua  vera 
in  its  entire  circumference.  During  the  fourth  month  the  cap- 
sularis unites  at  all  points  to  the  vera  and  its  nourishment  ceases 
except  at  its  oase.  The  area  where  capsularis  at  its  base  joins  the 
serotina  and  vera  is  known  as  the  Border  Zone  and  constitutes  the 
boundary  of  the  ' ' placental  area"  in  the  first  three  months.  The 
base  of  the  capsularis  unites  last  with  the  vera.  Septa  of  serotinal 
decidua  extend  between  villi  and  groups  of  villi,  especially  at 
the  point  where  capsularis,  serotina,  and  vera  join,  and  there 
lie  close  to  the  membrana  chorii,  forming  a  maternal  border  or 
margin  to  the  placenta — i.e.,  at  the  border  zone  the  decidua  is 
supposed  to  extend  up  to  and  touch  the  membrana  chorii  as 
Winkler 's  Plate. 

In  the  early  three  months,  up  to  the  formation  of  the  placenta, 
even  though  the  uterus  grows  actively,  the  growing  chorion  fron- 
dosum  and  the  base  of  the  chorion  Jaeve  extend  into  vera  and  split 
it  into  two  layers  ( ?).  The  lower  layer  becomes  serotina  and  the 
upper  layer  is  added  to  the  capsularis.  From  the  end  of  the 
third  month  on,  the  uterus  enlarges  passively  through  growth  of 
the  ovum.  It  is  scarcely  possible  that  the  edge  of  the  growing 
placenta  then  likewise  splits  the  vera  into  two  layers  to  any  ex- 
tent, but  in  its  growth  it  will  extend,  strictly  speaking,  not  upon 
vera,  but  upon  the  base  of  the  capsularis  which  has  united  to 
vera.  The  villi  do  not  atrophy  on  every  point  of  the  capsularis. 
They  may  persist  on  the  part  of  the  capsularis  nearest  to  the  vera 
and  serotina.  When  capsularis  unites  to  vera  these  villi  may 
grow  through  the  united  capsularis  and  vera.  As  a  rule  the 
loosest  union  between  capsularis  and  vera  is  at  this  point  and  so 
the  loosest  union  of  villi  and  placenta  to  decidua  is  at  this  point. 

Three  groups  are  observed  in  mammalia,  as  regards  the  char- 
acter of  the  chorion. 

(1)  The  chorion  is  smooth  and  is  attached  to  the  uterine  mu- 
cosa, which  is  rich  in  vessels.  The  chorion  takes  from  the  large 
epithelial  cells  of  the  uterus  nourishment  for  the  embryo. 

(2)  The  chorion  has  projections  or  villi.  An  allantois  ap- 
proaches the  chorion,  and  contained  umbilical  vessels  enter  the 
villi.  The  chorion  and  the  mucosa  are  closely  connected.  In  the 
pig,  for  instance,  numerous  projections,  rich  in  vessels,  fit  into 
smooth  depressions  in  the  mucosa,  in  which  open  the  uterine 


THE  PLACENTA. 


95 


Co 


Uterine  wall. 


Dccidua. 


Placenta.      '^ 


Fig.  43. — Low-pressure  drawing  of  uterus  and  placenta  at  full  term,  showing 
the  close  but  uneven  attachment  of  the  placenta,  two-thirds  of  actual  thickness. 
To  the  right  the  villi  are  on  the  muscularis.  To  the  left  (marked  Decidua)  there 
is  spongiosa.  In  hardening  a  separation  formed  between  compacta  and  spongiosa 
at  this  point. 


U.W. 


•«~-3' 


V,it 


U.W. 


is 


i^ 


U.W. 


few  .^.■■■;  ;■  ■•■■??  If  &'&■■:  \<$ 


Pi 


FiZK. 


Fig.  44. — Utero-placental  junction  at  full  term.  8  and  the  other  spaces  are 
maternal  vessels.  Villi  are  projecting  into  maternal  sinuses.  U.W.,  uterine 
wall  infiltrated  with  fetal  cells,  especially  with  the  very  dark  giant  syncytial 
masses.  Of  the  four  septa  between  the  villi,  the  two  outer  are  "adherent  villi," 
the  two  inner  are  decidual  septa.  Some  of  the  sinuses  are  possibly  glands  with 
lost  epithelium. 


96 


THE  PLACENTA. 


glands.     In  labor  the  villi  and  the  uterine  mucosa  are  separated 
without  loss  of  mucosa  substance. 

(3)  At  one  or  more  parts  of  the  chorion  a  placenta  develops 
composed  of  placenta  fetalis  and  placenta  uterina.  In  the  sheep, 
cow,  and  ruminants  a  subdivision  exists.     Numerous  small  pla- 


Fetal 
giant  masses 


Group  of  villi  in 
a  vein. 


Mat.  vein. 


Mat.  vein. 

Fetal  cells  brealdnf, 

through  tissue 
between  two  veins. 


Villus  in  a  vein. 

Fig.  45. — High-power  drawing  of  an  area  in  Fig.  44,  showing  the  invasion  of 
maternal  tissue  by  fetal  cells  even  at  full  term,  and  also  the  entrance  of  villi 
into  the  uterine  veins  through  the  blood  current. 

centre  or  cotyledones  are  present.  The  villi  are  covered  with  flat 
cells  and  the  depressions  of  mucosa  are  lined  by  cylindrical  cells. 
The  latter  develop  a  so-called  uterine  milk  for  the  nourishment 
of  the  fetus.  All  other  mammalia  with  a  placenta  evidence  a 
very  close  connection  betiveen  the  maternal  and  fetal  parts,  and 


Fig.  46. — High-power  drawing  of  placental  villi  of  Fig.  44,  showing  the  free 
syncytial  masses  and  the  chorionic  syncytium  to  be  identical  with  the  syncytial 
giant  masses  of  Fig.  45. 


in  labor  a  decidua  is  cast  off.     Here  a  syncytium  forms  the  sep- 
aration between  the  villi  and  the  maternal  blood. 

The  invading  trophoblast  and  syncytial  cells  have  a  decided 
poiver  of  wandering.  These  wandering  cells  are  often  found 
singly,  entering  between  the  muscle  and  the  connective-tissue 
bundles,  in  the  lymph  spaces  and  often  in  the  blood  vessels. 


THE  PLACENTA.  97 

Through  pressure  they  are  often  reduced  to  thin,  long,  spindle- 
shaped  forms,  and,  when  found,  the  muscle  fibres  between  appear 
to  be  changed  forms  of  the  latter.  In  the  earlier  periods,  round 
or  polyhedral  cells  with  very  large,  round  or  irregular,  long, 
darkly-staining  nuclei  are  found  and  have  been  generally  mis- 
taken for  decidua  cells.  Their  nuclei  are  often  very  large  and  on 
degeneration  contain  vacuoles.1 

In  the  specimens  (Figs.  43,  44)  on  page  95  is  seen  a  section 
through  a  placenta  and  the  uterine  wall  at  full  term.  The  villi 
are  very  closely  grouped.  The  uterine  wall  evidences  large 
sinuses  and  is  thoroughly  infiltrated  with  fetal  cells  and  many 
giant  syncytial  masses1  of  the  same  character  as  the  syncytial  cov- 
ering of  the  villi.  In  the  drawing  may  be  seen  four  extensions 
between  the  uterine  wall  and  the  main  mass  of  the  placenta.  Be- 
tween the  extensions  loose  and  attached  villi,  as  well  as  free  syn- 
cytial masses,  are  present.  The  two  middle  extensions  belong  to 
the  uterine  wall,  but  they  are  thoroughly  infiltrated  with  fetal 
cells.  On  their  sides  and  at  their  tips  villi  are  attached,  sending 
at  these  points  their  cells  in  the  uterine  wall. 

The  two  outer  extensions  are  the  so-called  adherent  villi  firmly 
embedded  in  the  uterine  wall,  and  their  tips  are  outlined  by  more 
closely  grouped  and  more  darkly  stained  ectodermal  cells.  It  is 
from  points  like  these  that  the  ectodermal  cells  and  the  giant 
cells  invade  most  deeply  the  uterine  wall,  as  may  be  seen  in  Fig. 
44.  The  spaces  between  these  extensions  represent  the  mouths 
of  the  maternal  sinuses  which  send  their  blood  into  the  inter- 
villous space. 

In  the  case  of  normal  uterine  gestation  villi  do  not  project  into 
the  arterial  openings  of  the  intervillous  space.  They  do,  how- 
ever, project  normally  not  only  at  the  border  sinuses,  but  at  all 
the  serotinal  points  into  the  veins  alone.  The  villi  are  of  normal 
structure  and  often  so  numerous  that  they  occlude  the  vein 
lumina.  They  are  frequently  very  long  and  follow  the  course 
of  the  veins  for  a  considerable  distance,  so  that  in  the  uterus  villi 
may  be  found  in  direct  contact  with  the  uterine  muscle  or,  better, 
in  the  veins  of  the  uterine  muscle  (Fig.  45). 

From  the  very  earliest  period  of  trophoblastic  development 
trophoblast  cells  may  be  carried  into  the  maternal  circulation 
through  the  blood  lacuna?  and  the  blood  capillaries.  In  the  latter 
stages  the  trophoblast  cells  invading  the  decidua,  eroding  the 

*Many  consider  these  placental  giant  cells  to  be  of  decidual  origin 
So  does  Spee. 

7 


98  THE  PLACENTA. 

vessels,  and  destroying  the  decidua  furnish  still  further  op- 
portunities for  the  entrance  of  fetal  cells  into  the  maternal  cir- 
culation. When  the  intervillous  space  is  well  defined  and  is 
limited  in  its  entire  circumference  by  the  point  of  union  of  the 
decidua  vera  and  the  capsularis  (decidua  refiexa),  a  still  further 
opportunity  is  furnished  to  syncytial  masses,  cell  groups,  and 
even  villi  to  be  carried  through  the  veins  into  the  maternal  cir- 
culation. In  the  still  later  periods  and  at  full  term,  villi  pro- 
jecting into  the  maternal  veins  may  be  carried  off,  and  the  fetal 
cells  which  have  invaded  the  decidua  and  the  uterine  Avail,  and 
which  even  up  to  the  last  days  of  gestation  continue  to  enter  the 
maternal  vessels,  may  readily  enter  the  maternal  blood  current. 
In  eclampsia  such  elements  have  so  frequently  been  found  in  the 
cirsulation,  and  especially  in  the  lungs,  that  they  have  been 
considered  the  cause  of  this  affection.  They  have,  however,  been 
proved  to  be  rather  the  result  than  the  cause,  for  Schmorl  and 
others  have  found  them  in  these  locations  in  perfectly  normal 
cases. 

The  important  fact  remains  that  from  the  very  earliest  mo- 
ment, not  only  in  the  primary  intervillous  space  but  in  the  fully- 
formed  intervillous  space,  as  well  as  through  the  vessels  of  the 
uterine  decidua  and  ivall,  fetal  cells  are  continually  entering  the 
blood  of  the  mother. 


OHAPTEE  XIII. 

THE    UMBILICAL    VESSELS    AND    CORD. 

A.    UMBILICAL   VESSELS. 

The  ovum  possesses  its  fluid  centre  or  yolk.  It  may  possess 
a  covering  of  discus  proligerus  and  albumin.  On  embedding 
the  trophoblast  digests  the  decidual  cells  and  is  surrounded  by 
the  so-called  symplasmatic  fluid.  The  ovum  develops  and  the 
trophoblast  grows.  During  this  time  osmosis  and  the  yolk  are 
sources  of  nourishment. 

As  the  decidua  is  invaded  capillaries  are  opened,  and  in  the 
first  few  days  trophoblast  is  acted  on  by  blood  of  the  mother. 
It  changes  trophoblast  cells  to  syncytium  and  probably  blood 
elements  enter  into  the  composition  of  the  cells.  Osmosis  again 
serves  to  explain  the  growth  of  the  ovum  and  its  contents.  On 
the  interior  of  the  ovum  we  have  the  embryo,  consisting  of  ecto- 
derm, mesoderm,  and  a  lining  of  entoderm,  which  entodermal  lin- 
ing is  a  part  of  the  entoderm  of  the  yolk  sac  and  abdominal 
vesicle.  The  ectoderm  of  the  embryo,  consisting  of  stratified 
epithelium,  is  continued  into  the  single-layered  amnion  reflected 
over  its  dorsal  aspect.  The  contents  of  the  yolk  sac  thus  line  the 
entoderm  of  the  embryo.  A  branch  of  the  entoderm  extends  into 
the  abdominal  adherent  band  as  the  allantoic  duct  (Figs.30cZ,46&). 

As  the  ventral  and  caudal  ends  curve  anteriorly,  and  the  lateral 
walls  also,  they  constrict  the  abdominal  vesicle.  The  connection 
between  extra-abdominal  umbilical  vesicle  and  intra-abdominal 
is  through  a  resulting  narrow  canal,  the  ductus  omphalo-entericus 
(Fig.  46  a  and  b).  The  duct  is  called  omphalo-entericus  because 
meanwhile  mesoderm  and  entoderm  have  formed  intestine  and  the 
duct  enters  into  intestine  instead  of  into  a  flat  entodermal  lining 
of  the  embryo.  All  this  while  arteries  and  veins  have  developed 
on  the  abdominal  vesicle,  the  arterise  and  vena?  omphalo-mesen- 
tericse.  The  arteries  pass  from  the  aorta  to  the  vesicle,  the  veins 
from  the  vesicle  to  the  venous  end  of  the  heart  tube.  In  the  first 
month  develop  two  umbilical  arteries  and  two  umbilical  veins. 
The  arteries  are  branches  of  the  aorta.     They  pass  along  the 


100  THE  UMBILICAL  VESSELS  AND  CORD. 

future  lateral  pelvic  walls,  along  the  later  bladder,  along  the 
later  anterior  abdominal  wall  to  the  adherent  band  of  mesoderm. 
Two  umbilical  veins  develop,  one  of  which  atrophies.  Their  con- 
tents at  first  enter  through  the  duct  of  Cuvier  into  the  heart. 

The  two  venae  omphalo-mesenterica?  pass  along  the  intestine 
and  anastomose  at  the  duodenum.  They  send  branches  to  the 
budding  liver,  the  future  hepatic  veins.  These  pass  into  the  end 
area  of  the  venae  omphalo-mesentericse  which  empties  into  the 
primitive  heart.  The  liver  grows  and  thus  needs  more  blood. 
Then  develop  the  umbilical  veins,  which  pass  through  the  ducts 
of  Cuvier  to  the  venous  sinus  of  the  heart,  passing  over  the  liver. 
The  right  vein  atrophies.  Some  branches  of  the  left  umbilical 
vein  anastomose  under  the  liver  with  the  vena?  omphalo-mesen- 
terica;.  This  anastomosis  under  the  liver  soon  becomes  the  im- 
portant part  and  finally  takes  all  the  placental  blood  to  the  liver 
and  through  the  hepatic  veins.  Thus  the  umbilical  blood  cir- 
culates with  the  yolk  blood  through  the  liver  and  then  through 
the  yolk  veins  to  the  heart,  for  the  end  piece  of  the  yolk  veins  be- 
comes the  cardiac  end  of  the  future  inferior  vena  cava.  At 
first  the  umbilical  vessels  are  small,  while  the  omphalo-mesen- 
teric  are  large.  As  the  yoke  is  sucked  up  the  omphalo-mesen- 
teric  vessels  atrophy  and  the  umbilical  grow.  The  branches 
of  the  latter  extend  on  through  the  abdominal  pedicle,  through 
the  mesoderm  of  the  membrana  chorii  into  the  villi,  and  join  the 
capillaries  there.  At  the  end  of  the  first  month  the  fetal  heart 
begins  to  beat,  and  in  the  first  month  circulation  through  the 
vessels  begins,  and  for  the  first  time  there  is  an  exchange  be- 
tween maternal  blood  and  the  contents  of  the  chorionic  vessels 
through  the  syncytium  and  cells  of  Langhans.  As  the  liver 
grows  the  yolk  veins  atrophy  and  the  umbilical  veins  grow 
larger.  "When  the  liver  can  no  longer  take  care  of  all  the  placen- 
tal blood  the  ductus  venosus  Aurantii  is  formed,  and  so  part 
of  the  blood  goes  directly  into  the  inferior  vena  cava.  The 
original  yolk  veins  form  the  portal  circulation,  which  becomes 
active  in  the  latter  part  of  the  fetal  nine  months.  After  birth 
the  portal  circulation,  carrying  blood  from  the  intestines,  pan- 
creas, and  spleen,  supplies  the  liver.  The  portal  circulation,  as 
said  before,  develops  from  the  yolk  veins.  These  changes  are 
due  to  the  change  in  size  and  importance  of  the  yolk,  placenta, 
and  liver.  After  birth  the  umbilical  vein  becomes  the  ligamentum 
teres  of  the  liver;  the  ductus  venosus  becomes  the  ligamentum 
venosum  (Hertwig). 


THE  UMBILICAL  VESSELS  AND  CORD. 


101 


B.    THE   UMBILICAL    CORD. 

The  ductus  omphalo-entericus  enters  the  future  ileum  a1  a 
point  lying  subsequently  near  the  cecum.  It  is  obliterated  in  the 
eighth  week  and  disappears.  Sometimes  it  is  retained  and  is 
known  as  the  diverticulum  of  Meckel.  It  may  be  simply  a 
diverticulum  of  the  ileum.  It  may  extend  up  to  the  umbilicus  as 
a  patent  canal  extending  from  the  ileum.  It  may  remain  as  a 
band  extending  between  the  ileum  and  the  umbilicus. 

The  umbilical  artery  of  each  side  forms  from  its  first  part  the 
common  iliac.  The  remainder  passing  along  the  pelvic  lateral 
wall  to  the  side  of  the  bladder,  along  the  anterior  surface  of  the 
abdominal  wall  to  the  adherent  band  and  umbilicus,  becomes 
the  ligamentum  vesico-umbilieale  laterale.     The  intra-abdominal 


Fig.  46a. — Embryo  with  abdominal  mesodermal  pedicle  and  with  umbilical  vesi- 
cle, showing  amnion  still  close  to  the  embryo,  a  condition  still  found  in  the  third 
week  or  even  later.    (Ahlfeld.) 


portion  of  the  allantoic  duct  becomes  a  part  of  the  bladder  and 
the  urachus,  which  extends  from  the  summit  of  the  bladder  along 
the  anterior  abdominal  wall  to  the  navel. 

Of  the  umbilical  veins,  one  atrophies.  Early  in  its  career 
it  joins  the  veme  omphalo-mesenterica?,  which,  in  their  later 
stages,  are  connected  with  the  liver,  and  thus  it  enters  the  liver 
and  subsequently  becomes  the  ligamentum  teres.  Coming  out  of 
the  abdomen  of  the  fetus  are : 

1.  The  adherent  band  of  mesoderm. 

2.  In  it  the  allantoic  duct. 

3.  In  it  the  umbilical  vein  and  umbilical  arteries. 

4.  The  atrophied  umbilical  vesicle  and  its  duct,  the  omphalo- 
enteric  duct. 

5.  On  the  latter  the  atrophied  omphalo-mesenterie  vessels. 


102 


THE  UMBILICAL  VESSELS  AND  CORD. 


C.    AMNION. 

The  amnion,  even  in  the  third  week,  may  lie  close  upon  the 
fetus.  In  it  fluid  is  secreted  which  constantly  distends  it.  As 
the  cephalic  and  caudal  ends  take  on  a  ventral  curve,  and  as  the 
lateral  walls  of  the  germinal  plate  curve  upward  and  gradually 
approach,  and  as  the  points  from  which  amnion  begins  thus  ap- 
proach, the  amnion  comes  nearer  and  closer  to  the  abdominal 
pedicle  and  the  omphalo-enteric  duct.  "When  the  amnion  is  fin- 
ally distended  so  that  it  is  in  contact  with  the  inner  lining  of 
the  membrana  chorii  (6th-10th  week),  it  must  envelop  the  ab- 
dominal pedicle  and  the  atrophied  umbilical  vesicle.     The  vesicle 


Allantoic  duct 
(Urachus) 


Cloaca 


Fig.  466. — Ovum  (schematic),  showing  extra-embryonal  chorion  connected  with 
the  embryonal  area  by  the  mesoblastic  umbilical  pedicle.  In  the  umbilical  pedicle 
are  the  allantoic  duct  and  the  umbilical  vessels.  Passing  from  the  umbilical 
vesicle  to  the  intestine  are  the  omphalo-enteric  duct  and  its  obliterated  vessels. 
When  the  amnion  becomes  large  enough  to  line  the  membrana  chorii  (sixth  weevc 
or  later),  it  presses  these  structures  together  and  surrounds  the  then-formed 
umbilical  cord. 

is  longer  than  the  abdominal  pedicle,  so  that  its  tip  lies  for  a  dis- 
tance on  the  fetal  surface  of  the  membrana  chorii.  The  point 
of  attachment  of  the  original  adherent  band  to  the  membrana 
chorii  is  the  point  of  attachment  of  the  abdominal  pedicle  to  the 
chorion  frondosum  and  the  point  of  attachment  of  the  umbilical 
cord  to  the  placenta.  At  the  umbilicus  the  amnion,  which  thus 
covers  the  cord,  goes  over  into  the  abdominal  epidermis.  The 
main  substance  of  the'cord  consists  of  "Wharton's  jelly.  A  long, 
thin  cord  is  characteristic  of  man. 


CHAPTER  XIV. 
GROSS    ANATOMY    OF    THE    PLACENTA. 

The  placenta  is  a  thickly  spongy,  fairly  circular  mass  measur- 
ing 15-20  centimetres  in  diameter  and  about  3-4  centimetres  in 
thickness.  The  surface  toward  the  embryo  has  attached  to  it  the 
cord  and  is  covered,  or  rather  lined,  with  the  amnion. 

Placenta  is  the  finally  developed  membrana  chorii  of  the 
chorion  frondosum  with  its  myriads  of  chorionic  villi.  Instead 
of  each  villus  being  connected  with  the  membrana  chorii,  we  have 
connected  with  the  latter  large  stems  on  which  are  numberless 
branches  and  sub-branches  covered  with  chorionic  villi. 

The  outer  surface  of  the  placenta  is  divided  by  furrows  into 
areas  or  islands  called  cotyledones.  A  cotyledo  consists  of  a 
stem  passing  out  from  the  membrana  chorii.  From  it  pass  villi 
and  large  branches  covered  with  villi,  and  from  these  still  smaller 
branches  with  villi.  The  uterine  placental  area  has  been  invaded 
by  trophoblast  cells  and  villi  during  a  period  of  nine  months,  so 
that  compacta  and  almost  all  of  the  spongiosa  have  been  "eaten 
up."  If,  from  a  certain  area,  we  remove  compacta  and  spon- 
giosa, we  pass  from  the  region  of  capillaries  toward  the  region  of 
vessels  situated  in  the  muscularis.  The  uterus,  however,  has 
grown  actively  in  the  first  three  months.  The  vessels  of  such  an 
area  have  hypertrophied  during  this  time  proportionately  with 
the  enlargement  and  hypertrophy  of  all  the  uterine  structures. 
In  the  next  six  months  the  uterus  enlarges  passively  and  a  further 
influence  is  exerted  on  the  openings  of  the  vessels  on  the  uterine 
surface — i.e.]  they  are  stretched  and  opened  in  trumpet  fashion. 
As  a  result,  we  find  on  the  uterine  placental  surface  larger  and 
smaller  sinuses  lined  more  or  less  with  endothelium,  which  endo- 
thelium may  extend  in  trumpet  fashion  to  various  degrees. 

Except  at  the  margin,  practically  no  glands  are  found  beneath 
the  decidual  projections.  The  remnant  of  decidua  covering  the 
uterine  placental  area  is  very  thin  and  is  so  infiltrated  with  fetal 
trophoblast  cells  as  to  be  practically  fetal  in  character.  The 
same  is  true  of  the  decidual  projections. 

The  sinuses  are  situated  in  hollows  or  depressions,  for  the 


104 


GROSS  ANATOMY  OF  THE  PLACENTA. 


Former  de- 
cidua  vet 


Glandularis 
or  spongiosa 

Compacta 


Menibrana  cliorii 


Amnion 


Umbilical  vessels 


Vessels  in 

villous  branch 
Vessels  in  large 
placental  stem 


Villi 
Membrana  cliorii 


Former  de-  (  Compacta 
cidua  vera    ) 

Spongiosa 


Maternal  vessel 
(capillary) 


Maternal  vessel 
(capillary) 


Gland  or  sinus 
in  serotina 


Decidual 
septum 


Decidual  "bay" 
filled  with  villi 


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GROSS  ANATOMY  OP  THE  PLACENTA.  105 

uterine  surface  is  very  irregular.  As  a  result  of  irregular  in- 
vasion by  trophoblast  cells  and  villi,  and  as  a  result  of  the  deeper 
invasion  by  the  "adherent  villi,"  the  uterine  surface  shows  ir- 
regular decidual  projections.  Between  these  projections  and  at 
their  base  are  the  "sinuses."  Numberless  individual  villi  are 
loosely  attached  to  the  tips  and  sides  of  the  projections.  Masses 
of  villi  fill  up  the  hollows  or  bays.  To  the  bottom  of  these  bays 
are  attached  the  adherent  villi — i.e.,  the  large  stems  which  pass 
off  from  the  membrana  chorii. 

The  attachment  of  stems  between  decidual  projections,  and  the 
extension  of  decidual  projections  between  masses  of  villi,  serve 
to  divide  off  the  uterine  surface  and  the  placenta  into  compart- 
ments. These  compartments  are  filled  solidly  with  villi.  As  a 
result  the  blood  coining  from  the  uterine  arteries  is  limited  more 
or  less  to  the  compartment  into  which  it  enters.  We  have  the  so- 
called  intervillous  spaces.  The  entire  placental  structure  is  not 
washed  or  infiltrated  by  all  the  maternal  blood  making  exit  from 
the  uterine  placental  surface,  but  by  the  blood  of  its  compart- 
ment. 

No  space  separates  external  placental  surface  from  uterine 
surface.  The  masses  of  villi  composing  the  placenta  have  the  most 
external  groups  close  to  the  openings  of  the  maternal  sinuses. 
Villi  and  masses  of  villi  extend  into  the  uterine  veins.  This  ar- 
rangement, whereby  maternal  blood  passes  out  between  the 
densely  grouped  villi  and  back  again  through  the  venous  sinuses 
of  compartments,  gives  the  greatest  and  most  plentiful  oppor- 
tunity of  surrounding  the  myriads  of  villi  with  maternal  blood. 
The  fetal  vessels  passing  through  the  cord,  through  the  mem- 
brana chorii,  through  the  villous  stems,  through  the  villous 
branches  into  every  villus,  give  a  tremendous  opportunity  for 
exchange  between  maternal  blood  and  fetal  blood  through  the 
syncytium. 

The  placenta  is  thus  well  attached  to  the  uterine  wall.  In  ad- 
dition the  reflexa  is  attached  to  the  vera  at  all  parts  of  its  per- 
iphery. In  addition  the  liquor  amnii  presses  placenta  and  re- 
flexa closely  against  serotinal  area  and  vera. 

At  the  edge  of  the  placenta  the  amnion  which  lines  it  passes 
on  and  lines  the  membrana  chorii  which  has  not  formed  placenta, 
the  chorion  lasve. 

From  the  edge  of  the  placenta  on,  the  membrana  chorii  or 
chorion  lgeve  is  attached  by  means  of  the  reflexa  to  the  decidua 
vera. 


106  GROSS  ANATOMY  OF  THE  PLACENTA. 

At  the  edge  of  the  placenta  the  attachment  of  reflexa  and  vera 
is  not  very  close.  This  area  represents  the  point  of  junction 
of  vera,  serotina,  and  reflexa.  After  union  of  base  of  reflexa  to 
vera  at  this  point,  the  edge  of  the  placenta  may  extend  on  upon 
the  reflexa,  now  united  to  vera.  Beyond  this  point  the  attach- 
ment of  chorion  to  vera  per  the  reflexa  is  the  same  as  at  other 
points.  The  uterine  wall  at  the  edge  of  the  placenta  has  at  all 
times  the  best-preserved  growth  of  glands,  for  here  the  attach- 
ment of  reflexa  and  vera  is  last  completed  and  the  pressure  is 
least. 

There  remains  of  the  decidua  only  a  thin  layer  at  best.  In 
some  areas  the  villi  are  practically  on  the  muscularis.  At  other 
points  spongiosa  is  preserved,  but  the  glands  have  lost  their 
epithelia  and  look  like  vessel  sinuses.  At  other  points  compacta 
and  spongiosa  are  fairly  well  preserved.  The  invasion  of  the 
decidua  is  very  irregular  in  character  (Fig.  43).  Generally 
speaking,  little  decidua  separates  the  villi  from  the  muscularis. 
The  layer  of  Nitabuch  said  to  separate  fetal  and  maternal 
structures,  and  probably  derived  from  fetal  ectoderm,  is  varying 
in  amount  and  regularity. 


PART  II. 

THE  ESSENTIALS  OF  TUBAL  GESTATION. 


CHAPTER  1. 

PROCESSES  ANTEDATING  TUBAL  GESTATION. 

Etiology. — In  former  years  our  views  concerning  the  origin 
of  ectopic  gestation  depended  mainly  on  the  discovery  of  patho- 
logical conditions  macroscopically  evident.  Cases  were  report- 
ed with  fibroma  of  the  isthmus  tubEe  or  with  polyps  at  the  uterine 
end  of  the  tube.  The  growth  of  the  ovum  in  a  tubal  diverticu- 
lum or  in  an  accessory  tube  was  considered  to  furnish  a  satis- 
factory etiology.  In  some  cases  the  pressure  of  ovarian  or 
abdominal  tumors  was  supposed  to  obstruct  the  onward  move- 
ment of  the  ovum.  Abel  and  Freund  found  in  a  twisting  of 
the  tube  and  in  a  failure  of  development  a  satisfactory  theory 
for  the  frequent  occurrence  of  ectopic  gestation.  Since,  in  a 
majority  of  such  cases,  peritoneal  adhesions  are  present,  these 
were,  and  even  yet  are,  considered  to  so  alter  the  course  of  the 
tube's  lumen  as  to  prevent  the  entrance  of  the  ovum  into  the 
uterus.  Therefore  visible  inflammations  were  considered  to  be 
the  important  etiological  element. 

During  my  labors  a  colleague  gave  me  a  specimen  of  extra- 
uterine gestation  combined  with  a  multilocular  serous  ova- 
rian cyst,  with  the  request  that  I  should  find,  if  possible,  a  Graaf- 
ian follicle  in  the  ovary,  though  he  believed  none  to  be  pres- 
ent. I  considered  that  this  specimen  would  furnish  a  proof 
of  external  migration  of  the  ovum,  and  that  this  migration  might 
stand  in  an  etiological  relation  to  the  ectopic  gestation.  Ex- 
amination of  the  ovarian  cyst  showed  no  Graafian  follicle. 
Therefore  the  ovum  had  come  by  external  migration  from  the 
other  ovary.  In  Case  3  the  same  absence  of  a  Graafian  follicle 
was  noted. 

The  experiments  of  Leopold  have  shown  that  the  ovum  given 
off  by  one  ovary  may  enter  the  tube  of  the  other  side.  The  cases 
are  not  so  rare  in  which  the  tube  of  one  side  was  closed  or  ab- 
sent, and  although  the  corpus  luteum  verum  was  found  in  the 
ovary  of  the  same  side,  yet  the  ovum  was  found  in  the  uterus. 
Schroder,  Koblanck,  and  others  have  found  a  pregnancy  in  a 
rudimentary  horn  between  which  and  the  uterus  no  epithelial 


110  PROCESSES  ANTEDATING  TUBAL  GESTATION. 

connection  existed.  Manierre  has  collected  39  cases  of  preg- 
nancy in  rudimentary  horns.  The  same  is  true  of  those  cases 
in  which  the  corpus  luteum  verum  is  on  one  side  and  the  ovum 
has  developed  in  the  horn  of  a  uterus  unicornis  of  the  opposite 
side.  Kustner  removed  a  right-sided  extrauterine  gestation  sac 
"and  a  left-sided  ovarian  cyst.  Shortly  after  a  uterine  pregnancy 
"took  place. 

,  ■■External  migration  occurs  frequently  in  tubal  gestation. 
'Although  Kustner  took  note  of  the  frequency  of  this  event  in 
only  the  la'st  25  of  a  series  of  100  cases,  he  found  it  to  have  taken 
place  in  seven.  Prochownik  found  that  external  migration  had 
taken  place  in  one  case  of  eight  which  he  had  examined  closely. 
Martin  found  the  corpus  luteum  on  the  same  side  as  the  tubal 
gestation  in  thirty-seven  cases,  on  the  opposite  side  in  four,  and 
uncertain  in  thirty-six. 

External  migration  of  the  ovum  has  been  viewed  by  Sippel 
and  others  as  the  etiological  factor.  They  believe  that  the  ovum 
in  its  migration  becomes  too  large  to  permit  of  its  passage 
through  the  tube  lumen.  The  examinations  of  Peters,  however, 
show  conclusively  that  no  chorionic  villi  are  present  until  the 
ovum  has  been  nourished  for  a  considerable  time  by  the  decidua 
in  which  it  is  embedded.  In  addition  the  Graafian  follicle  is 
in  the  majority  of  instances  found  in  the  ovary  of  the  affected 
side,  so  that  such  an  etiology  would  explain  only  the  smaller 
number  of  cases. 

This  migration,  however,  calls  our  attention  to  the  presence 
of  a  pathological  condition  in  the  mucous  membrane  of  the 
opposite  tube.  While  it  calls  our  attention  to  the  fact  that  the 
other  tube  is  affected,  it  only  proves  that  it  is  more  affected  than 
the  tube  in  which  the  ovum  is  finally  embedded,  for  some  cilia 
must  be  present  in  the  latter  to  influence  the  external  migration 
of  the  ovum.  Various  experiments  make  it  seem  probable  that  in 
the  perfectly  normal  tube  no  ovum  can  develop. 

Kustner,  in  his  experiments  on  rabbits,  extirpated  one  ovary 
and  extirpated  or  tied  off  the  uterine  horn  of  the  other  side.  In 
these  attempts  no  extrauterine  gestation  resulted.  However, 
since  such  a  pathological  point  of  development  of  the  ovum  does 
occur  in  animals,  a  satisfactory  explanation  of  the  failure  of 
these  attempts  could  not  be  found  until  the  experiments  of 
Mandl  and  Schmit  were  published.  In  their  work  upon  animals 
they  found  the  following  to  be  the  case :  After  coitus,  and  after 
the  lapse  of  time  sufficient  to  permit  union  between  the  ovum 


PROCESSES  ANTEDATING  TUBAL  GESTATION.  Ill 

and  the  spermatozoa  at  the  abdominal  end  of  the  tube,  they  tied 
off  the  tube  at  the  uterine  end.  '  Their  results  were  negative.  No 
tubal  gestation  resulted.  When,  however,  the  uterine  horn  was 
tied  off  a  pregnancy  in  this  horn  resulted,  showing  that  the  liga- 
tion was  not  the  disturbing  factor  and  that  in  all  probability 
ova  do  not  develop  on  a  normal  tubal  mucosa. 

In  considering  the  history  of  those  cases  which  have  been 
closely  noted,  it  is  found  that  ectopic  gestation  occurs  most  fre- 
quently in  multipara?  and  that  a  sterile  period  of  varying  length 
precedes  this  pathological  development.  Martin  found  that  65 
multipara?  were  affected  as  compared  with  20  nullipara?.  In  a 
series  of  100  cases  of  Kiistner's,  only  10  ectopic  gestations  oc- 
curred in  nullipara?.  The  other  87  had  borne  children  and  3 
had  aborted.  In  24  cases  it  occurred  five  or  more  years  after 
the  last  labor ;  in  55  cases,  from  one  to  five  years  after ;  and  in 
8,  in  less  than  twelve  months.  Veit  found  that  in  52  cases  of 
repeated  ectopic  gestation  a  sterile  period  of  two  to  eleven  years 
preceded  the  occurrence  of  this  process.  Between  the  two  events 
was  a  period  of  six  weeks  to  six  years.  This  sterile  period  repre- 
sents the  time  in  which  inflammatory  changes  in  the  mucosa  may 
occur,  either  gonorrheal,  puerperal,  or  tubercular.  These 
changes  naturally  involve  the  uterine  end  of  the  tube  more  than 
the  abdominal,  and  in  the  subsequent  course  of  events,  when 
healing  does  result,  the  uterine  end  improves  slowly.  What 
are,  then,  the  pathological  changes  in  the  tubal  mucosa  which 
stand  in  an  etiological  relation  to  ectopic  gestation? 

In  a  series  of  8  closely  examined  cases  Prochownik  found  a 
gonorrheal  history  three  times;  in  one  of  these  cases  there  was 
an  acute  gonorrheal  affection  of  the  pregnant  tube.  Moskowicz 
found  that  of  two  cases  tuberculosis  was  the  etiological  factor  in 
one,  and  that  in  the  other  gonococci  and  staphylococci  were 
present  in  the  pyosalpinx  of  the  non-pregnant  tube.  Median  to 
the  ovum  Veit  found  microscopical  changes  which  represent  the 
results  of  pus  inflammation.  In  two  cases  Diihrssen  found  cilia 
abdominal  to  the  ovum,  but  none  toward  the  uterine  end.  Kiist- 
ner  observed  very  frequently  a  hemorrhagic  tendency  of  the 
non-affected  tube,  showing  that  tube  at  least  to  have  been  ab- 
normal. I  found  in  three  cases  distinct  changes  in  the  mucosa 
median  to  the  ovum. 

Franz  makes  inflammatory  changes  in  the  tubes  responsible  for 
the  occurrence  of  ectopic  gestation.  This  is  the  more  probable 
since  inflammatory  processes  are  so  frequently  found  in  the 


112  PROCESSES  ANTEDATING  TUBAL  GESTATION. 

other  tube.  Franz  found  such  changes  in  eighty  per  cent  of  these 
cases  in  which  a  sterile  period  of  two  to  seventeen  years  was 
noted..  In  cases  where  a  sterile  period  of  less  than  two  years  was 
observed  tubal  changes  of  the  other  side  were  present  in  only 
53  per  cent.  He  comes  to  the  conclusion  that  we  must  seek  the 
etiology  in  those  affections  of  the  tubes  which  have  run  their 
course,  and  which,  having  for  a  long  time  prevented  the  moving 
of  the  ovum,  have  permitted  a  gradual  and  partial  restoration  to 
normal  conditions. 

While  in  a  certain  number  of  cases  no  pathological  microscopic 
changes  are  found  in  the  tubal  mucosa,  it  may  be  explained  by 
the  fact  that  so-called  catarrhal  conditions  frequently  show  little 
microscopical  change.  Even  during  or  after  gonorrhea  the  tube 
may  seem  microscopically  perfectly  normal.  Ahlfeld,  in  an  ex- 
perience of  many  years  at  the  University  of  Marburg,  met  with 
so  few  cases  of  tubal  gestation  that  he  considers  the  relative  free- 
dom of  his  patients  from  gonorrhea,  as  compared  with  those  in 
the  larger  cities,  to  be  the  only  explanation. 

Various  inflammatory  influences  are  etiological  factors  in  that 
they  destroy  the  cilia  in  whole  or  in  part  or  diminish  their  func- 
tional activity.  Besides,  from  the  experiments  made  on  ani- 
mals we  know  that  absence  or  early  atrophy  of  the  ovaries  in- 
fluences the  muscular  development  and  the  functional  activity 
of  the  uterine  wall  and  the  structure  of  the  mucous  membrane 
and  the  cilia.  In  cases  of  functional  interference  with  the  se- 
cretion of  the  ovary,  or  in  the  atrophy  subsequent  to  labor  or 
as  the  result  of  lactation  or  of  constitutional  disturbances  or  of 
failures  of  development,  the  activity  of  the  cilia  is  diminished. 

Naturally  there  must  be  activity  to  a  certain  extent  on  the  part 
of  the  cilia,  especially  at  the  abdominal  end  of  the  tube,  for 
extrauterine  gestation  occurs  most  frequently  in  the  isthmus 
tubas.  Prochownik  found  an  ampullar  location  in  only  3  cases 
out  of  45.  Mandl  and  Schmit  found  in  69  cases  an  ampullar 
situation  in  only  15.  Diihrssen  found  an  isthmic  location  in 
all  of  his  29  patients.  In  the  5  cases  which  I  have  examined 
closely  the  same  is  true.  Although  Mercier  has  collected  30 
cases  of  interstitial  gestation  (with  rupture),  Leopold  10  cases  of 
ovarian  gestation  ( ? ) ,  and  although  the  growth  of  an  ovum  on 
the  fimbriae,  as  well  as  tubo-ovarian  pregnancies,  occurs,  yet  the 
vast  majority  are  found  near  the  uterine  end  of  the  tube. 

A  further  proof  may  be  found  in  the  fact  that  recurrences 
of   tubal   gestation   take   place   but   rarely  in   the   same   tube. 


PROCESSES  ANTEDATING  TUBAL  GESTATION.  113 

Patellani,  in  a  tabulation  of  36  cases,  found  that  first  one  tube 
and  then  the  other  was  the  seat  of  development.  Veit  in  52 
cases  found  that  it  recurred  only  three  times  in  the  same  side. 
An  additional  point  of  importance  is  the  occurrence  of  tubal 
gestation  in  either  tube  at  the  same  time,  of  which  Gebhardt 
mentions  9  cases.  Further,  Patellani  has  collected  37  instances 
of  combined  uterine  and  extrauterine  gestation— a  practical 
proof  of  an  affection  of  one  tube,  and  certainly  excluding  ex- 
ternal migration. 

I  believe  that  in  the  so-called  sterile  period  gonorrheal. 
puerperal,  tubercular,  and  atrophic  processes  take  place.  The 
interval  of  years  between  the  last  labor  and  the  ectopic  ges- 
tation, the  fact  that  the  location  is  generally  in  the  middle  area 
of  the  tube,  the  fact  that  repeated  gestations  are  observed  and 
rarely  in  the  same  tube,  the  occurrence  of  an  ectopic  gestation  on 
both  sides  at  the  same  time,  and  the  frequency  of  external  migra- 
tion together  with  a  combination  of  extra-  and  intrauterine  ges- 
tation, point  certainly  to  an  affection  of  one  tube  and  probably, 
but  to  a  lesser  degree,  of  the  other  tube.  The  frequency  with 
which,  according  to  Kiistner,  a  hemorrhagic  tendency  of  the  non- 
affected  side  occurs,  as  well  as  the  microscopic  discovery  of  catar- 
rhal conditions,  together  with  the  history  and  the  microscopical 
evidence  of  the  presence  of  gonococci,  point  distinctly  to  a  tubal 
affection.  The  observation  of  Duhrssen,  who  found  cilia  ab- 
dominal to  the  placental  site  and  none  median  to  it,  and  Veit's 
observation  of  the  presence  of  inflammation  median  to  the  ovum, 
as  well  as  the  theory  of  congenital  and  acquired  atrophy  of  the 
tube,  especially  subsequent  to  labor,  lead  us  at  the  present  day 
to  seek  in  the  microscopical  changes  of  the  tubal  mucosa,  the  in- 
jury to  the  cilia,  the  etiological  factor  in  tubal  gestation. 


CHAPTER  II. 

VARYING  VIEWS  CONCERNING  THE  HISTOLOGY  OF 
TUBAL  GESTATION. 

The  Decidua. — In  the  uterus  the  ovum  descends  by  a  centrif- 
ugal process  into  a  well-developed  decidua,  which  is  gradually 
divided  into  a  superficial  compact  layer  and  a  deeper  spongy 
glandular  layer.  Concerning  the  existence  of  a  tubal  decidua, 
however,  opinions  differ.  Webster's  view  that  a  compacta  and 
spongiosa  are  formed  receives  no  support.  Wyder  found,  in  one 
case,  decidua  in  the  periphery  of  the  region  occupied  by  the 
ovum.  Mandl  describes  decidua  cells  in  the  placental  area, 
while  Veit  found  decidua  cells  not  only  at  the  placental  site  but 
at  a  distance  from  it  on  the  opposite  wall.  In  his  eight  closely 
examined  cases  Prochownik  describes  decidua  cells  and  in  one  a 
well-developed  decidua.  Abel  found  a  well-marked  decidua 
about  an  ovum,  especially  in  the  region  of  the  placenta.  His 
statement  is  positive,  since  he  compared  it  microscopically  with 
the  decidua  cast  out  from  the  uterus. 

On  the  other  hand,  Aschoff  found  none  at  the  placental  site. 
Kiihne  describes  only  a  pseudo-decidua  consisting  of  fibrin,  con- 
nective tissue,  and  invading  ectoderm  cells.  Though  slight  de- 
cidual changes  may  occur  at  the  placental  area,  the  cells  which 
have  been  previously  described  as  decidual  are  considered  by 
him  to  be  the  cells  of  Langhans,  and  the  same  vieiv  is  shared  by 
Aschoff  and  Ulesko-Stroganoiva.  In  most  cases  fibrin  masses, 
blood,  villi,  and  cells  which  at  least  look  like  decidua  cells,  but 
which  many  consider  to  be  trophoblast  cells,  are  to  be  found.  It 
is  a  fact,  however,  that  at  the  area  of  greatest  pressure  the  so- 
called  decidua  is  often  thinned  to  a  decided  extent. 

Veit  in  turn  considers  the  so-called  cells  of  Langhans  to  be, 
in  the  peripheral  areas,  decidual  cells.  Though  he  finds  cells  of 
the  layer  of  Langhans  in  the  maternal  vessels,  yet  they  are  not 
connected  with  like  cells  about  the  vessels.  There  is  an  absence 
of  like  cells  between  the  vessels  and  the  serotinal  surface.  While 
granting  that  the  resemblance  is  great,  he  considers  those  inter- 
stitial cells  present  in  the  peripheral  areas  about  the  ovum  to  be 


HISTOLOGY -OF  TUBAL  GESTATION.  115 

decidual,  and  concludes  that  the  connective  tissue  in  the  circum- 
ference of  the  intervillous  space  in  tubal  gestation  undergoes 
decidual  change,  only  that  this  layer  is  very  much  thinner  than 
in  the  uterus. 

Embedding  of  the  Ovum,  and  the  Reflexa  or  Capsularis. — A 
considerable  difference  of  opinion  exists  as  regards  the  reflexa. 
Wyder  found  none  in  his  case  and  the  ovum  was  only  loosely  at- 
tached. Abel  found  no  capsularis  and  most  of  the  villi  were 
free  and  only  few  were  adherent.  "Werth  described  sections  of 
a  tube  in  which  the  ovum  had  settled  at  the  height  of  a  tubal 
fold.  Werth  described,  in  another  case,  a  capside  containing 
muscle  fibres  passing  out  at  the  base  from  the  muscular  fibres  of 
the  tube  wall.  The  external  covering  of  the  capsule  consisted  of 
epithelium.  According  to  Kreisch,  the  capside  may  consist  of 
united  folds.  He  described  the  presence  of  a  reflexa  in  three 
cases,  however,  which  was  not  composed  of  tubal  folds.  In  a 
specimen  examined  eight  days  after  conception  a  reflexa  was 
found  by  him.  The  formation  of  a  pseudo-reflexa  readily  takes 
place  if  the  ovum  is  embedded  in  a  thick  system  of  folds.  Others 
believe  that  in  many  cases  a  capsule  consisting  of  longitudinal 
muscle  fibres  and  mucosa,  with  no  epithelium  on  the  inner  side,  is 
of  frequent  occurrence. 

Asehoff  and  Fiith  make  it  evident  that  the  ovum  makes  its 
way  down  into  the  mucosa,  as  is  the  case  in  the  uterus,  and  that 
it  extends  even  further  deeply  into  the  muscular  wall.  It  is 
then  covered  laterally  by  the  inner  layers  of  the  muscularis  and 
by  the  mucosa,  which  are  pushed  over  it,  forming  a  capsularis 
and  bounding  the  intervillous  space.  In  several  closely  exam- 
ined cases  the  ovum  has  been  found  almost  under  the  entire 
thickness  of  the  tubal  wall,  lying  directly  on  the  vessels  of  the 
ligamentum  latum.  Muscle  fibres  are  absent,  however,  at  the 
summit  of  this  resulting  capsule.  In  another  case  the  ovum  was 
nearly  extratubal,  lying  between  the  muscularis  of  the  tube  and 
the  muscle  fibres  of  the  ligamentum  latum.  The  ovum  was,  of 
course,  separated  from  the  lumen  by  the  mucosa  and  by  muscle 
fibres.  At  the  apex  of  this  capsularis  there  was  considerable 
thinning,  but  the  epithelium  upon  the  mucosa  was  intact.  Such 
a  development  would  explain  the  so-called  pseudo-intraliga- 
mentous  cases  of  Kiistner.  The  capsule  has  been  found  in  some 
cases  to  be  lined  with  the  cells  of  Langhans. 

Intervillous  Space. — If  the  capsule  be  composed  of  folds,  ac- 
cording to  Kreisch,  they  may  be  so  firmly  united  that  an  inter- 


116  HISTOLOGY  OF  TUBAL -GESTATION. 

villous  space  may  exist.  In  Abel's  case  the  space  between  the 
chorion  frondosum  and  the  decidua  was  larger  than  at  any  other 
point;  adherent  villi  extended  into  the  decidua,  bnt  most  of  the 
villi  were  found  free  in  the  space.  The  vessels  of  the  decidua 
opened  directly  into  these  intervillous  spaces,  which  contained 
blood.  According  to  Aschoff,  the  centrifugal  descent  of  the 
ovum  makes  the  existence  of  an  intervillous  space  easy.  Veit, 
in  a  well-preserved  non-interrupted  case,  found  a  well-developed 
intervillous  space  in  which  Mood  circulated,  and  traced  a  vein 
containing  villi  into  this  common  intervillous  space.  Ktihne,  on 
the  other  hand,  considers  the  invasion  of  the  blood  vessels  by  the 
villi  to  be  pathological,  and  does  not  consider  the  existence  of  an 
intervillous  space  probable,  because  in  eight  cases  he  found  no 
reflexa.  Since  Von  Both  collected  84  cases  of  ectopic  gestation 
with  viable  fetus,  an  intervillous  space  must  have  been  present. 

Villi. — Abel,  as  stated  before,  finds  a  decidua  vera  in  the  per- 
ipheral areas  of  the  ovum ;  the  villi,  however,  he  found  to  extend 
only  up  to  the  muscle.  Leopold  and  others,  on  the  contrary,  find 
the  villi  extending  deeply  into  the  muscular  ivall  of  the  tube. 
The  villi  are  covered  with  two  layers.  At  their  ends  are  pillar- 
like groups  of  cells  growing  into  the  wall,  between  the  muscle 
fibres,  and  representing  extensions  of  the  trophoblast.  The  cells 
of  Langhans  growing  into  the  muscle  and  uniting  with  it  form 
the  so-called  Saugeplatle.  It  is  with  this  layer  that  the  villi  unite 
through  the  cell  groups  found  at  the  ends.  These  complexes  of 
cells  of  Langhans  and  syncytium  speak  for  the  fetal  nature  of 
the  latter,  and  the  pillar-like  groups  are  simply  groups  of  tro- 
phoblast not  yet  reached  by  the  mesoderm. 

Abel  found  most  of  the  villi  free  and  only  some  adherent  to 
the  decidua.  As  they  did  not  enter  into  the  muscle,  the  connec- 
tion was  not  a  close  one.  Wyder  removed  an  ovulum  in  its  en- 
tirety from  a  tube  and  later  examination  showed  no  villi  extend- 
ing through  the  decidua  to  the  muscle.  Kuhne,  Ulesko-Stro- 
ganowa,  and  others  find  that  the  cells  of  Langhans  extend  active- 
ly into  the  submucous  tissue  and  into  the  muscle  bundles,  and 
believe  that  these  are  the  cells  which  are  often  mistaken  for  de- 
cidual cells.  It  is  upon  them,  as  upon  the  compacta  of  the 
uterus,  that  the  villi  grow.  At  the  same  time,  they  may  extend 
entirely  up  to  the  serosa  of  the  tube. 

As  just  mentioned,  the  villi  may  extend  up  to  the  serosa,  and 
perforations  of  the  wall  covered  by  thrombi  have  been  frequently 
found.     Kuhne  describes  cells  which  have  entered  the  serotinai 


HISTOLOGY  OP  TUBAL  GESTATION.  117 

veins.  In  the  vessel  spaces  under  the  pseudo-decidua  he  finds 
free  cells  whose  character  proves  them  to  be  pseudo-decidual 
elements.  He  considers  these  cells  to  have  entered  through  the 
vessel  walls.  Mandl  found  decidual  cells  in  the  vessels  and  be- 
lieves that  they  have  passed  out  of  the  surrounding  tissue  into 
the  lumen.  Other  cells  in  the  same  location  he  views  as  prolif- 
erated endothelium.  Cornil  found  syncytial  elements  in  the  ves- 
sels and  considers  them  decidual  cells  which  have  entered  through 
the  vessel  walls.  Other  investigators  hold  that  the  cells  of  Lang- 
hans  grow  directly  into  the  submucous  tissue  and  into  the  muscle 
bundles,  and  that  these  cells  may  penetrate  the  vessels  and  open 
them  as  in  the  uterine  compacta.  They  describe  the  villi  as  fol- 
lowing the  course  of  these  cells  of  Langhans  into  the  muscularis, 
up  to  the  serosa  and  through  the  serosa,  which  latter  perfora- 
tions are  usually  covered  by  thrombi.  Aschoff,  Ulesko-Strogan- 
owa,  Leopold,  and  others  have  described  villi  as  perforating  the 
vessel  walls. 

Deportation. — By  Veit  a  quite  different  theory  is  given,  how- 
ever, to  explain  the  presence  of  fetal  cells  and  villi  in  the  muscu- 
lar wall  of  the  tube.  In  discussing  the  relation  of  the  ovum  to 
the  uterus,  Heinz  considers  that  the  fetal  tissues  grow  into  the 
maternal  structures  and  says  that  the  maternal  glands,  vessel 
ivalls,  and  tissues  are  eaten  up  by  the  villi.  Cornil  considers  that 
the  ovum  in  an  extrauterine  gestation  not  only  does  the  same, 
but  follows  a  course  resembling  that  of  a  uterine  chorioma. 
AVhile  Veit  may  grant  the  correctness  of  such  a  view  in  patho- 
logical conditions,  he  does  not  believe  it  justifiable  to  consider  it 
the  usual  course. 

In  the  case  of  a  normal  uterine  gestation,  villi  do  not  project 
into  the  arterial  openings  of  the  intervillous  space.  They  do, 
however,  project  normally,  not  only  in  the  border  sinuses  but  at 
all  the  serotinal  points,  into  the  veins  alone.  The  villi  are  of 
normal  structure  and  often  so  numerous  that  they  occlude  the 
vein  lumina.  They  are  frequently  very  long  and  follow  the 
course  of  the  veins  to  a  considerable  distance.  In  the  uterus, 
villi  are  thus  found  in  direct  contact  with  the  uterine  muscle, 
or,  better,  in  the  veins  of  the  uterine  muscle.  The  same  is  true  in 
tubal  gestation.  Whether  this  occurs  in  all  cases  or  not  cannot 
be  positively  stated  (Veit). 

Veit  believes  that  cells  in  the  periphery  of  the  ovum  enter 
at  an  early  period  into  the  peripheral  veins.  In  normal  gesta- 
tion the  uterus  grows  as  much  as  the  ovum  needs,  and  the  ovum 


118  HISTOLOGY  OF  TUBAL  GESTATION. 

as  much  as  the  uterus  permits.  Later,  as  soon  as  the  ovum  in 
the  uterus  has  attained  a  certain  size  and  the  edge  of  the  placenta 
extends  laterally,  another  process  is  added  to  that  of  general 
growth.  This  process  is  brought  about  by  the  villi  which  pro- 
ject into  the  serotinal  veins.  If  a  villus  enters  a  vein  it  generally 
remains  in  contact  with  the  periphery  of  the  ovum  and  grows 
further  in  its  length  as  well  as  in  its  circumference.  In  its 
growth  it  dilates  the  lumen  of  the  vein  so  decidedly  that  its 
serotinal  portion  is  everted  and  taken  up  into  the  general  inter- 
villous space.  On  either  side  endothelium  then  extends  for  a 
short  distance  upon  the  serotinal  surface.  In  the  uterus,  nor- 
mally, only  cells  of  the  ovum  or  of  the  villi  are  loosened  and 
pass  on  into  the  veins,  but  the  villi  themselves,  as  a  rule,  remain 
in  contact  with  the  ovum.  In  uterine  gestation  the  entire  endo- 
metrium becomes  deciduous,  and,  therefore,  decidua  cells  are 
found  in  the  periphery  of  these  vessels  which  contain  villi. 
In  the  peripheral  region  of  the  well-preserved  tubal  sac  Veit 
found  free  villi  in  a  vein.  Series  sections  showed  this  vein  to  en- 
ter into  the  intervillous  space.  Therefore  the  villi  were  no  longer 
connected  with  the  ovum.  This  occurrence,  whereby  syncytium 
and  villi,  loosened  from  all  connection  with  the  ovum,  are  found 
in  the  veins,  is  given  by  Veit  the  name  deportation. 

Veit,  then,  explains  the  descriptions  of  Aschoff,  Fiith,  Cornil, 
and  Ulesko-Stroganowa,  who  find  a  destruction  of  the  tube  wall 
and  an  invasion  of  vessels  by  the  villi,  on  the  theory  of  deporta- 
tion through  the  veins. 

Veit  does  not  believe  that  the  fetal  cells  possess  the  power  of 
wandering,  because  he  finds  the  cells  of  Langhans  in  a  vessel 
but  no  such  cells  about  it.  Therefore,  in  his  opinion,  the  cells 
have  not  perforated  the  vessel  because  none  are  present  in  the 
connective  tissue.  Veit,  however,  forgets  that,  in  addition  to  de- 
portation, a  wandering  of  cells  and  a  perforation  of  the  vessels 
does  occur. 

Veit  denies  that  the  cells  of  the  ovum  wander  into  the  connec- 
tive tissue.  We  know  that  cell  groups  go  gradually  over  into 
the  cells  of  Langhans  on  the  villi,  while  on  the  other  side  they  are 
either  separated  from  the  decidua  by  fibrin,  or  else  the  cells  pass 
gradually  into  the  decidua  with  such  a  resemblance  to  the  latter 
cells  that  it  is  difficult  to  differentiate  them. 

Veit  does  not  believe  that  the  cells  of  Langhans  in  the  per- 
iphery of  the  tube  look  different  from  those  which  are  near  the 
villi.     He  found  at  the  area  of  the  tubal  vera  a  few  changed 


HISTOLOGY  OF  TUBAL  GESTATION.  119 

connective-tissue  cells  and  considers  them  to  be  a  beginning 
stage  of  a  decidua  vera.  In  the  periphery  he  saw  cells  about  the 
vessels  differing  somewhat  in  appearance  and  stain  from  the 
cells  of  Langhans,  and,  since  they  are  like  the  above-mentioned 
vera  cells,  he  considers  them  decidual.  In  this  connection  he 
overlooks  the  power  of  the  trophoblast. 

Where  the  cell  groups  enter  the  decidua  he  sees  a  certain  form 
of  cells.  At  other  points  where,  in  series,  sections,  no  villi  enter 
the  serotina  he  finds  the  same  cells.  Therefore  either  the  cells 
of  Langhans  can  wander  in  all  directions  or  else  a  decidual 
change  is  present,  and  he  believes  the  latter  to  be  the  case  and 
states  that  a  decidua  exists,  but  much  less  than  in  the  uterus. 

Conclusions. — In  the  uterus  there  takes  place  a  centrifugal 
descent  of  the  ovum  on  a  spot  free  of  epithelium.  The  compact 
layer  of  the  decidua  forms  the  enveloping  zone.  There  is  an 
early  connection  between  the  maternal  Mood  and  the  fetal  cells  in 
the  form  of  a  trophoblast  which  is  a  product  of  the  ectoderm. 
The  trophoblast,  at  points,  extends  far  into  the  compacta  and 
the  cells  have  a  decided  power  of  wandering.  The  trophoblast 
is  changed  to  syncytium  through  the  corrosive  action  of  the 
blood.  The  opening  of  the  maternal  vessels  occurs  even  before 
villi  are  formed,  and  at  this  and  at  all  subsequent  stages  fetal 
cells  enter  the  maternal  circulation.  The  primary  enveloping 
zone  becomes  the  subsequent  intervillous  space.  Neither  the 
uterine  epithelium  nor  the  maternal  endothelium  play  any  part 
in  the  formation  of  the  syncytium.  No  reflexa  is  formed,  but 
through  the  descent  of  the  ovum  a  capsularis  results.  The  ovum, 
through  its  trophoblast  cells  and  villi,  invades  and  destroys  the 
maternal  decidua.  The  fibrin  layer  of  Nitabuch  and  the  thick- 
ness of  the  decidua  prevent  the  extension  of  the  villi  too  deeply 
into  the  wall. 

In  the  tube  we  find  no  division  into  two  layers,  as  is  the  normal 
in  the  uterus.  In  fact,  no  decidua  is  formed.  There  is  an  ab- 
sence of  the  thin-walled  decidual  vessels,  and  the  muscularis,  if 
at  all,  is  only  slightly  hypertrophied.  We  are  only  anticipating 
the  results  of  our  investigations  when  we  say  that,  with  the  ex- 
ception of  the  absence  of  the  decidua  and  an  enveloping  zona 
composed  of  compacta,  the  processes  of  gestation  in  the  tube  are 
the  same  as  those  in  the  uterus,  modified  only,  as  we  ivoidd 
naturally  expect,  by  the  absence  of  the  decidua  and  the  thin- 
ness of  the  tube  wall. 

The  varying  differences  of  opinion  are  due  to  five  causes : 


120  HISTOLOGY  OF  TUBAL  GESTATION. 

1.  Ova  of  different  states  of  preservation  have  given,  quite 
naturally,  different  pictures. 

2.  Ova  of  very  different  ages  have  been  described  and  com- 
pared without  taking  this  fact  into  consideration. 

3.  As  in  the  uterus,  but  even  more  so,  the  differentiation  be- 
tween fetal  and  maternal  cells  has  been  almost  overlooked,  so 
that  trophoblast  cells  have  been  viewed  as  decidual.  The  ability 
of  the  fetal  cells  to  wander,  to  invade  the  tube  wall,  and  to  per- 
forate the  vessels  has  been  granted  by  only  a  few  investigators. 

4.  The  fact  that  there  are  several  forms  which  the  ovum  fol- 
lows in  its  embedding  in  the  tube  has  almost  entirely  escaped 
attention. 

5.  "While  Veit's  deportation  is  an  accepted  fact,  he  leaves  out 
of  consideration  the  processes  of  "cell  wandering"  and  "vessel 
invasion." 

How  nearly  and  how  closely  in  all  important  details  the  his- 
tology of  tubal  gestation  may  resemble  the  course  of  uterine  ges- 
tation, will  be  seen  in  the  following  pages. 


OHAPTEE  III. 

EMBEDDING  OF  THE  OVUM  AND  DEVELOPMENT  OF 
EXTRA-EMBRYONAL  STRUCTURES. 

Of  the  cases  examined  in  series  sections,  these  three  are  taken 
as  types  representing  the  important  forms  and  stages. 

I.      THE    COLUMNAR    TYPE   OP   TUBAL   GESTATION. 

The  following  specimen  (Fig.  47)  presents  an  oval  body, 
measuring  one-third  of  a  centimetre  in  its  greatest  diameter, 
situated  on  the  mucous  folds  of  a  tube  removed  because  of  the 


_;._ ; .  Coagulum 

of  ovum 

Larw  ■■   W7  ±— Tubal 

half  of         —   - — : • — - 

ovum  At. ".: 


mucosa 


Tube 

wall 


..w  - 


Fig.  47. — Very  young  ovum  situated  on  the  tip  of  the  folds  of  the  tubal  mucosa 
in  a  case  of  ectopic  gestation  accompanied  by  an  old  intraperitoneal  hemorrhage. 

diagnosis  of  ectopic  gestation  (on  operation  the  abdomen  con- 
tained clotted  blood).  The  tube  was  stained  in  toto,  embedded 
in  celloidin,  and  cut  in  series  sections.  Fifty  slides  from  the 
middle  area  of  the  tube  contain  sections  of  this  oval-shaped  struc- 
ture (Fig.  47a).  A  section  through  its  greatest  diameter  shows 
it  to  be  composed  of  two  unequal  halves :  a  smaller  half  consisting 


122  EMBEDDING  OF  THE  OVUM. 

of  a  blood  coagulum,  and  a  larger  half  composed  of  closely 
grouped  cells,  of  protoplasmatic  cells  and  masses  containing  one 
or  more  nuclei,  and  of  villi.  Villi  are  also  found,  but  sparsely, 
about  the  coagulum  (Fig.  48). 

Sections  through  the  smaller  diameters  show  the  coagulum 
diminishing  in  size  and  extent,  with  an  actual  and  relative  in- 
crease in  the  extent  and  area  composed  of  closely  grouped  cells 


i'  >  *        TT 


Fig.  47a. — Ovum  of  Fig.  47,  showing  division  into  two  halves  and  an  intimate 
connection  with  the  tubal  mucosa  on  the  right.  (Section  through  the  greatest 
diameter.) 

and  villi,  furnishing,  then,  a  centre  composed  of  cells  and  a 
periphery  in  which  are  villi  (Fig.  49). 

The  more  external  sections  are  continually  smaller  (Fig.  50), 
and  the  central  cell  area  diminishes  in  size,  so  that  the  small  and 
most  external  sections  present  only  villi  (Fig.  51).  In  all  the 
sections  the  villi  are  in  the  periphery  of  the  centrally  situated 
closely  grouped  cells. 

By  reconstruction,  then,  we  obtain  a  solid,  oval-shaped  body 
possessing  a  covering  composed  of  protoplasmatic  cells  and  villi. 
Within  this  covering  are  closely  grouped  cells,  and  in  the  in- 
terior, although  eccentrically  situated,  is  the  coagulum.  We  are 
dealing  with  an  ovum  (?)  in  which  the  amnion,  umbilical  vesicle, 
and  the  central  cavity  are  obliterated  by  blood,  while  the  tro- 
phoblast  and  villi  are  preserved.     This  ovum,  as  we  may  view  it, 


EMBEDDING  OF  THE  OVUM. 


123 


is  adherent  on  one  side  to  folds  of  mucosa  which  evidence  a 
proliferation    of   their   epithelial   covering.     On   the   epithelial 


.  ■  .  >,m, 


JUS 


\ 

.  -  J 


Fig.  48. — Another  section  through  ovum  of  Fig.  47,  showing  in  one  half  tro- 
phoblast  cells,  villi,  and  very  dark  syncytial  masses. 

covering,  and  between  the  folds,  are  rows  of  round,  structure- 
less bodies  densely  grouped,  and  the  same  are  found  at  numer- 
ous points  covering  the  ovum,  except  at  the  end  opposite  to  the 


■  % 


Fig.   49. — A  more  peripheral   section,   showing  trophoblast  cells  and  villi  and 
very  little  of  the  blood  coagulum. 

coagulum.  In  other  words,  on  and  between  the  mucosa  folds  in 
contact  with  the  ovum  is  seen  a  plasmatic  substance  distinctly 
excreted  by  the  epithelium,  and  in  it  are  also  red  blood  cells  and 
leucocyte  nuclei. 


124  EMBEDDING  OF  THE  OVUM. 

The  tube  wall  facing  the  other  end  of  the  ovum  presents 
mucosa  folds,  whose  epithelium  is  interrupted  at  various  points, 
while  at  other  points  are  proliferations  of  epithelium  and  round 
cells.  The  stroma  of  many  of  the  folds  is  absent,  while  others 
possess  dilated  capillaries  and  vessels,  and  still  others  are  filled 
with  blood  extravasations.  The  tube  wall  itself  is  covered  with 
epithelium,  and  in  the  wall  are  extravasations  of  blood,  and 
dilated  arteries  and  veins.  At  no  point  in  the  tube  wall  or  in 
the  mucosa  is  there  any  decidual  change  or  any  condition  repre- 
senting an  entrance  of  trophoblast  cells  or  of  villi.  The  ovum 
is  surrounded  by  a  plasmatic  substance  which  I  have  observed 
on  uterine  and  cervical  polyps  covered  with  epithelium  and  in 
active  growth.  It  is  not  a  deposit  from  the  blood,  as  such,  but 
one  actively  secreted  or  produced.  This  same  element  is  found 
on  the  mucosa  folds  in  immediate  contact  with  the  ovum.     The 


4V. 


Fig.  50. — A  still   more  peripheral   section,   showing  only  villi. 

adhesion  of  the  ovum  at  these  points  is  a  firm  one.  It  is  well 
preserved  and  therefore  in  active  contact  with  some  nutrition- 
producing  tissue.  The  shape  and  character  of  the  oval  body, 
together  with  its  other  characteristics,  prove  it  beyond  doubt  to 
be  an  ovum.  If  not  entirely  surrounded  by  the  tips  ofx  the 
mucosa  folds,  it  was  probably  situated  among  them  near  the 
tube  wall,  but  not  on  or  in  the  wall. 

The  other  end,  with  the  numerous  trophoblast  cells,  plasmodial 
elements,  and  villi,  was  probably  surrounded,  too,  by  mucosa  folds, 
and  here,  too,  an  intervillous  space,  containing  blood  coming  from 
the  capillaries  of  the  mucosa,  was  probably  present.  Although  we 
shall  see  that  this  end  was  infiltrated  by  maternal  blood,  I  cannot 
forbear,  in  this  connection,  to  mention  the  possibility  that  the 
ovum  obtained  nutrition  from  the  epithelium  of  the  mucosa  at 
the  point  of  adhesion,  which  represents  to  me  the  reflexa  or 
capsularis  composed  of  tubal  folds. 


EMBEDDING  OP  THE  OVUM. 


125 


(In  the  placenta  of  many  animals  it  is  found  that  the  blood 
extravasated  from  the  uterine  vessels  is  made  use  of  by  the  fetus, 
in  that  the  degenerating  products  of  the  extravasated  blood  cells 
are  taken  up  and  absorbed  by  the  ectoderm  cells.  According  to 
Strahl,  in  Galago,  a  Madagascar  lemuride,  numerous  extravasa- 
tions are  found  in  the  uterine  mucous  membrane,  and  their 
products  lie  in  the  connective  tissue  in  the  form  of  larger  and 
smaller  yellow  granules.  The  epithelia  of  the  glands  near  this 
extravasated  blood  are  more  or  less  filled  with  granules  re- 
sembling these.  He  considers  them  to  be  rests  of  the  blood  cells 
which  are  taken  up  by  the  gland  epithelium  and  made  use  of  by 
the  latter  in  furnishing  an  iron-containing  secretion.  The  gland 
epithelia  here  perform  a  function  which  in  other  placenta?  is  per- 
formed by  the  fetal  ectoderm.     In  Galago  fetal  villi  are  always 


1,. 


Fig.  51. — Most  peripheral  section,  showing  a  villus  only. 

in  contact  with  the  uterine  epithelium  and  obtain  nourishment 
from  it.  Between  the  uterine  epithelium  and  the  epithelium  of 
the  villi  are  seen  strands  which  represent  the  uterine  milk  taken 
up  by  the  villi.  Thus  the  fetus  gains  the  greatest  portion  of  its 
nourishment  through  the  chorionic  epithelium.) 

The  main  cell  body  is  composed  of  cells,  without  distinct  cell 
boundaries,  containing  nuclei  of  varying  form  and  staining 
darkly.  At  various  points  are  found  paler  cells  with  a  distinct 
nuclear  membrane  which  unite  in  groups  of  three  or  more.  More 
external,  in  the  region  of  the  villi,  the  cells  are  more  distinct  and 
the  nuclear  membrane  is  more  clear  and  nucleoli  can  be  distinctly 
seen  (Fig.  52).  The  more  external  these  cells  are  found  the 
larger  and  the  more  swollen  and  the  paler  do  they  become,  and  a 
homogeneous  intercellular  substance  is  present.  In  the  centre 
of  those  sections  where  the  cells  are  so  densely  grouped  (Fig.  49) 
are  minute,  darkly-staining  granules  whose  identity  at  first  was 
not  distinct.     In  the  more  peripheral  areas,  however,  their  char- 


126  EMBEDDING  OF  THE  OVUM. 

acter  is  evident ;  for  they  are  only  found  where  red  blood  cells  are 
present  and  they  are  therefore  leucocyte  nuclei.  The  nearer  we 
approach  the  circumference  the  more  do  we  find  blood  in  the  in- 
terstices between  the  cells,  at  first  as  isolated  cells  or  groups,  and 
later  in  larger  spaces  containing  red  blood  cells.  Wherever  blood 
in  small  amount  is  present,  the  cell  nuclei  become  dark  and 
change  their  form,  becoming  long  spindle-shaped,  arranged  in 
single  strands  or  in  longer  parallel  groups.  "Where,  however, 
blood  in  larger  amounts  is  present,  protoplasmatic  masses  contain- 
ing numerous  round  or  spindle  nuclei  may  be  observed.     Near  the 


Youno  <£&* 
villus    *■' 


Fig.  52. — An  area  from  Fig.  48,  showing  trophoblast  cells,  their  transition  to 
the  chorionic  epithelium  in  the  upper  part,  and  to  syncytial  groups  in  the  lower 
part. 

circumference  the  number  and  extent  of  the  round  protoplas- 
matic groups  and  the  number  of  the  darker  or  longer  spindle- 
shaped  nuclei  increase,  and  the  latter  seem  to  invade  the  sections 
described  from  the  exterior  toward  the  interior.  In  the  ex- 
terior of  the  sections  are  villi  covered  with  a  double  layer  of 
thin  syncytium  with  flat  nuclei.  The  centre  is  composed  of  em- 
bryonal connective  tissue  staining  blue  and  containing  branching 
cells  (Fig.  52).  Other  villi,  some  of  which  are  quite  long,  have  a 
centre  composed  of  round  nuclei  with  nucleoli  which  are  very 
closely  grouped,  and  transitions  from  these  cells  to  syncytium  may 
be  distinctly  observed,  as  in  Fig.  52.  These  villi,  as  well  as  the 
others,  are  found  only  in  the  external  area  or  near  the  coagulum. 
Knobs  of  syncytium  and  so-called  syncytial  giant  cells  are  pres- 


EMBEDDING  OF  THE  OVUM. 


127 


ent  about  these  villi,  connected  by  a  pedicle  or  lying  apart.  In 
the  central  areas  no  connective  tissue  can  be  observed.  In  the  ex- 
ternal layers,  however,  as  said  before,  it  is,  evident  in  the  form  of 
a  structureless  substance  between  the  cells,  giving  these  areas  a 
pale  appearance  (Fig.  52).  It  is  not  present  in  the  younger  villi 
and  is  only  evident  in  the  fully  formed  ones. 


Blood  and  fibrin  at  area 
of  serotina 


Dilated  vessels  of  the 
tube  wall 


'r 


Tubal  lining 
covered  with 
fibrin 


Fig.  53. — Section  of  tube,  showing  normal  mucosa  in  the  lower  and  left  area, 
while  above  and  to  the  right  is  the  area  of  attachment  of  the  ovum,  giving  a 
typical  picture  of  the  tube  after  tubal  abortion. 


II.      THE   INTERCOLUMNAR   TYPE   OF    TUBAL   GESTATION. 

A  further  stage  of  development  of  a  tubal  ovum  is  well  rep- 
resented in  Fig.  53.  The  examination,  in  series  sections,  of  this 
specimen,  known  clinically  as  tubal  abortion,  divulges  numerous 
interesting  features.  One  half  of  the  circumference  of  the  tube 
lumen  is  of  a  normal  character;  the  other  half  is  in  a  torn,  in- 
filtrated condition  which  involves  not  only  the  mucosa  folds  but 
also  the  submucosa  up  to  the  muscularis.  Close  examination 
evidences  the  fact  that  the  ovum  was  situated  on  the  tube  wall, 
compressing  and  destroying  the  mucosa  folds  at  the  situation 
known  as  the  serotina.     On  either  side  of  this  point  the  mucosa 


128  EMBEDDING  OF  THE  OVUM. 

folds  were  evidently  united  about  the  ovum,  forming  a  pseudo- 
reflexa.  The  capillaries  and  large  vessels  at  the  serotinal  point 
are  filled  with  blood   (Fig.  53),  and  many  evidence  larger  or 

Muscular  fibres  of  tube  wall 


d 


mw^&m 


'Cell  group."  "* Jw&$ 


Trophoblast  cells 


wK^ 


Blood  clot 
and  fibrin 


Pig.  54. — Portion  of  serotinal  area  of  Pig.  53,  showing  pale  trophoblast  cells 
and  cell  groups  and  the  darker  syncytial  cells. 

smaller  injuries  and  invasions  of  the  wall.  At  the  serotinal  por- 
tion and  for  some  distance  on  either  side  is  observed  in  the  sub- 
mucosa  a  tissue  resembling  at  first  sight  decidua. 

On  close  examination  we  find  oval,  very  closely  grouped  cells, 

":■'  ,"/.:■■>&*■■  '.iiu 


■#:# 


Fig.   54a. — Typical  area  in  Pig.   54,  commonly  mistaken  for  decidua,  showing 
pale  trophoblast  cells  and  dark  syncytial  cells. 

consisting  mainly  of  nuclei  and  possessing  each  a  nucleolus  (Fig. 
54).  They  are  extremely  closely  grouped  and  between  them  are 
found  no  capillaries  or  spaces.  This  tissue  rests  not  only  on  the 
free  surface  of  the  tube  wall,  but  invades  it  at  many  points  to  a 


EMBEDDING   OP    THE   OVUM. 


129 


considerable  depth  (Fig.  55).  The  invasion  of  the  tube  wall  is 
not  an  even  one,  for  at  some  points  it  forms  a  continuous  deep 
layer  like  the  decidua,  at  other  points  it  enters  the  submucous 
tissue  in  irregular  branches  and  projections,  and  at  other  points, 
through  lateral  infiltration,  is  separated  from  the  free  surface  of 


Peritoneum 


y&fai 


t 


■  Muscularis 


WM 


blast 


Dense  group 
of  trophoblast 
veils,  representing 
a  "cell  group." 
as  found  at  the 
tip  of  the  villi 


Fig.  55. — Section  through  tube  wall  at  serotinal  area,  showing  the  paler  char- 
acter of  the  advanced  trophoblast  cells  and  the  darker  character  of  the  densely 
grouped  trophoblast  cells  near  the  ovum.  Typical  field  formerly  mistaken  for 
decidua,  but  differentiated  by  the  dark  spindle-shaped  syncytial  cells.  This  draw- 
ing shows  that  in  tubal  abortion  the  "rests"  are  of  the  same  nature  as  in  uterine 
abortion. 


the  tube  wall  by  a  considerable  space  of  normal  submucous  tis- 
sue. 

These  cells  are  found  about  the  smaller  and  the  larger  vessels, 
invading  and  infiltrating  their  muscular  walls  up  to  and  into  the 
lumen  of  the  vessel. 

The  character,  arrangement,  and  structure  of  these  cell  masses 
9 


130  EMBEDDING  OP  THE  OVUM. 

leave  no  doubt  that  they  are  trophoblast  cells.  In  addition  they 
may  be  identified  by  the  fact  that  at  almost  all  points,  especially 
those  points  near  the  inner  surface  of  the  tube,  they  are  ac- 
companied by  isolated,  long,  spindle-shaped  protoplasmatic  cells, 
by  groups  of  polynuclear  protoplasmatic  masses,  and  by  long, 
often  parallel  bands  of  the  same  character  (Figs.  54a  and  55a). 
These  are  the  syncytial  cells,  absolutely  identical  with  the  same 
elements  observed  in  all  the  previous  specimens,  especially  those 
seen  in  the  first  tubal  ovum. 

These  cells  may  be  further  identified  as  trophoblast  cells  by 
the  fact  that  they  are  found,  at  the  tip  of  some  adherent  villi, 


s 

m 


■\: 


W* 


«« 


Fig.  55a. — Another  area  from  Pig.  55,  showing  the  "advance  guard"  of  infil- 
trating trophoblast  and  syncytial  cells. 

extending  directly  into  the  tube  wall.  These  trophoblast  cells 
enter  into  the  submucosa  and  museularis,  forming  the  tissue 
which  so  many  investigators  have  called  decidua.  These  com- 
plexes of  trophoblast  and  syncytial  cells,  especially  the  groups 
found  at  the  tips  of  the  villi,  are  not  yet  filled  out  with  meso- 
derm, but  are  to  form  future  villi. 

At  no  point  do  the  connective-tissue  cells  of  the  tubal  folds  or 
of  the  submucosa  evidence  any  change  resembling,  in  the  slightest 
degree,  those  changes  occurring  in  the  uterine  mucosa  which  re- 
sult in  the  formation  of  decidua  cells. 

At  no  point  do  the  epithelial  cells  of  the  mucosa  evidence  any 
change  of  a  so-called  syncytial  character. 


EMBEDDING  OP  THE  OVUM. 


m 


III.      THE    CENTRIFUGAL   TYPE    OP    TUBAL    GESTATION. 

Figure  56  represents  a  tubal  gestation,  containing  a  fetus,  in 
the  sixth  or  seventh  week.  The  tube  wall  is  preserved  in  its  entire 
circumference,  with  the  exception  of  two  minute  areas  where  the 
chorionic  villi  have  actively  perforated  it.  Projecting  into  the 
dilated  lumen  of  the  tube,  and  almost  touching  the  mucous  lining, 
is  the  outer  covering  of  the  fetal  sac,  the  capsularis.  One  half  of 
the    circumference    of    the    tube    is    invaded,    infiltrated,    and 


Beginning  of 
reflexa  or 
capsularis 


Perforation 
■J  covered  by 
thrombus 


Capsulai 


Tube  loall 

Fig.   56. — Tubal   gestation   with   fetus   attached   by   umbilical    cord,    showing 
perforation  by  the  growing  villi  closed  by  a  thrombus. 


stretched  by  the  other  half  of  the  fetal  sac  wall,  that  is,  the  pla- 
centa. On  both  sides,  at  the  junction  between  the  infiltrated  tube 
wall  and  the  preserved  but  decidedly  stretched  tube  wall  which 
surrounds  that  half  of  the  fetal  sac  which  projects  into  the  tube 
lumen,  the  mucosa  of  the  latter  passes  over  upon  the  fetal  sae 
and  can  be  followed  upon  it  as  a  covering  of  the  latter  for  a 
certain  distance.  The  summit  of  the  sac  is  covered  by  a  tissue 
composed  of  fibrin,  trophoblast  cells,  leucocytes,  etc.  The  ovum 
possesses,  then,  a  capsularis  composed  in  part  of  fetal  folds  and 
submucosa.  This  capsularis  is,  strictly  speaking,  no  reflexa.  It 
must  be  called  a  pseudo-reflexa  or  capsularis. 

The  area  of  the  tube  circumference  entirely  filled  by  villi  is. 


132 


EMBEDDING  OP  THE  OVUM. 


the  true  placental  site,  and  here  is  found  a  real  intervillous  space 
bounded  on  all  sides  by  the  point  of  union  of  the  tube  wall  with 
the  base  of  the  capsularis.  The  remainder  of  the  circumference 
of  the  fetal  sac  evidences  villi,  but  the  space  between  the  cap- 
sularis and  the  inner  lining  of  the  sac  is  mainly  filled  with  blood 
and  blood  crystals.  At  the  real  placental  site  almost  no  rem- 
nants of  the  tube  wall  can  be  found.  At  this  half  of  the  tube 
wall  there  are  nothing  but  villi,  trophoblast  cells,  syncytial  cells, 
and  a  sea  of  maternal  blood  (Fig.  56a-). 

The  process  involved  in  this  invasion  of  the  tube  wall  and  the 


Tube  wall 


Tube  lumen 


Tube  ivall  going 
over  into  the 
capsularis  (reflexa) 


Eroded 
tube  ivall 


Villi  perforating 
tube  wall 


Pig.  56a. — Tubal  ovum  with  perfectly  developed  capsularis.  Tubal  wall  passes 
on  both  sides  over  into  the  capsularis.  Major  portion  of  placenta  is  at  the  lower 
border,  where  tubal  tissue  is  eroded  and  perforated  by  the  villi.  This  area  is  the 
intervillous  space.  Between  the  tube  lumen  and  the  central  cavity  of  the  ovum 
is  the  capsularis  filled  with  blood  and  blood  crystals. 

process  involved  in  the  formation  of  the  villi  can,  in  each 
section,  be  extremely  well  judged  on  either  side  at  the  point  of 
junction  of  the  capsularis  with  the  tube  wall  (Fig.  57).  Here, 
on  either  side,  there  extend  into  the  gradually  thinning  tissue 
of  the  tube  villi,  cell  groups,  and  syncytial  cells  which  invade  the 
muscularis  in  what  may  be  called  a  concentric  path.  We  ob- 
serve, at  the  tips  of  fully  formed  villi,  the  typical  trophoblast 
cell  groups.  We  see  them  extending  into  and  between  the 
muscular  fibres,  changing  into  and  accompanied  by  syncytial 


EMBEDDING  OP  THE  OVUM. 


133 


cells  and  masses  of  every  kind  and  form  yet  described  (Fig.  58). 
At  no  point  is  there  the  slightest  evidence  of  any  decidua  or  of 
any  decidual  reaction.  The  trophoblast  cells  invade  the  vessels 
of  the  tube  wall,  and  the  villi  themselves  enter  the  tube  wall 
and,  with  the  trophoblast  groups  at  their  tips,  enter  the  vessel 
lumina. 

At  the  main  placental  site  are  found  trophoblast  cells  with 
the  clearest  and  most  distinct  change  into  various  forms  of  inde- 
pendent syncytial  groups  and  into  the  syncytial  covering  of  the 


Tubal 
tissue 

passing  over 
into  capsularis 

Tubal  tissue 


Tube  wall 


Fig.  57. — Area  XX  of  Fig.  56a  magnified,  showing  the  reflexa  or  capsularis  and 
the  infiltration  and  invasion  of  the  tube  wall  by  the  trophoblast  and  villi. 

villi  (Fig.  58).  They  are  likewise  seen  to  pass  over  gradually 
into  the  layer  of  Langhans,  which  at  all  points  resembles,  the 
syncytial  layer  to  such  an  extent  that  it  might  be  said  that  the 
covering  of  the  villi  consists  of  a  double  layer  of  syncytial  cells 
(Fig.  59).  The  villi  have  actively  perforated  the  tube  wall  indi- 
vidually and  in  groups,  so  that  the  intervillous  space  communi- 
cated with  the  abdominal  cavity  at  these  points. 

This  stage  is  the  exact  macroscopic  and  microscopic  counter- 
part of  the  stage  seen  in  Fig.  39. 


134 


EMBEDDING  OF  THE  OVUM. 


If  no  interruption  take  place,  the  capsularis  unites  with  the 
mucosa  of  the  enveloping  tube  wall  in  the  same  way  that  this 
processes  exemplified  in  the  uterus. 

The  various  steps  in  the  succeeding  months  of  development  of 
a  tubal  gestation  may,  so  far  as  the  development  of  the  placenta, 
the  fetal  sac,  and  the  fetus  is  concerned,  be  considered  as 
identical  with  the  same  processes  in  the  uterus;  for  over  ninety 
cases  of  full-term  ectopic  gestation  with  viable  fetus  are  re- 
corded. 

The  various  steps  in  the  development  of  the  tubal  placenta, 


Blood  -form-  if  't ., ,  J? .  § 

ing  new t-^tiaj  f  ■ 


syncytium 
Syncytium TSyffij 


Syncytium 


Troplioblast 


Cell  group 


Stroma 
of  villus 


Syncytial 
mass 

Stroma 

with  nucleated 

reds 

Syncytial 

covering 

of  villus 


Fig.  58. — Area  of  advancing  trophoblast  cells  of  Fig.  57,  showing  transition  of 
trophoblast  cells  to  syncytial  groups  and  to  the  syncytial  covering  of  the  villi. 

depending  as  they  do  mainly  on  the  cells  of  the  ovum  itself,  the 
trophoblast  cells,  are  the  same  as  in  the  uterus.  The  differ- 
ence is  mainly  in  the  different  character  of  the  base  or  tropho- 
spongia.     We  may  draw  the  following  conclusions : 

(1)  In  tubal  gestation  no  decidua  or  trophospongia  develops. 
The  mucous  lining  of  the  uterus  is  really  a  lymph  tissue;  the  sub- 
mucosa  of  the  tube  is  not. 

(2)  Fetal  cells,  in  tubal  gestation,  may  at  any  time  enter  the 
maternal  circulation. 

(3)  As  regards  the  troplioblast,  the  syncytium,  the  villi,  the 
formation  of  blood  by  the  trophoblast  cells,  and  all  other  par- 


EMBEDDING  OF  THE  OVUM.  135 

ticulars,  the  processes  depending  on  and  originating  in  the  ovum 
are  the  same  in  both  uterus  and  tube. 

Certain  investigators  have  described  ova  embedded  in  the  tube 
wall,  where  a  capsularis,  was  present  containing  muscle  fibres 
passing  out  from  the  tube  wall  into  the  base  of  the  capsularis. 
The  ovum  was  found  entirely  under  the  entire  thickness  of  the 
tube  wall,  lying  on  the  vessels  of  the  ligamentum  latum— the  so- 
called  pseudo-intraligamentous  form. 

CONCLUSIONS. 

In  the  tube,  the  embedding  of  the  ovum  and  the  development 
of  the  placenta,  then,  is  found  to  follow  three  fairly  distinct 
forms:  (1)  the  columnar,  (2)  the  inter  columnar,  (3)  the  centri- 
fugal. 

Syncytium 
and  cells  of  ,,  „ 

Lunghans         .jgjgj  * 

"  *****»« 

Syncytium  **>  *& 


Tropho- 
blast 
cells 


Isolated 

syncytial 

cells 


Fig.  59. — Drawing  from  serotinal  area  of  Fig.  56a,  showing  trophoblast  cells 
going  over  into  isolated  syncytial  cells  and  into  syncytial  masses. 

1.  In  the  columnar  type  of  development  (Fig.  47)  the  ovum  is 
surrounded  by  mucosa  folds  only.  Here  an  invasion  of  the  capil- 
laries of  the  tubal  mucosa  occurs.  Such  a  columnar  situation 
makes  abortion  easy  and  of  little  danger.  Very  soon  after  the 
entrance  of  the  ovum  tubal  bleeding  may  result;  the  ovum  dies 
and  further  hemorrhage  expels  it.  The  tube  may  return  to  a 
normal  state  without  any  evidence  of  the  previous  condition,  or 
else  a  hematosalpinx  may  be  formed  if  the  abdominal  end  of  the 
tube  is  closed.  The  ovum  may,  theoretically,  develop  to  a  much 
further  degree  and  press  the  folds  against  the  tubal  wall.  If  de- 
velopment continues  the  villi  may  extend  into  it,  and  the  con- 
nection of  the  ovum  and  the  villi  with  the  surrounding  tissue  is 
a  loose  one,  as  in  the  case  of  Abel  and  of  Wyder  and  in  the 
specimen  Fig.  47. 


136  EMBEDDING  OF  THE  OVUM. 

2.  In  the  intercolumnar  form  (Fig.  53)  the  ovum  may  rest  on 
the  wall  of  the  tube.  Any  tubal  fold  beneath  it  will  be  com- 
pressed, but  epithelium  may  be  present  in  a  depression.  Other 
folds  may  form  a  capsularis,  which  consists  then  of  mucosa  alone ; 
if  such  a  capsularis  be  firm  an  intervillous  space  may  develop. 
The  villi  at  the  placental  site  enter  into  the  wall ;  here  a  hemor- 
rhage may  result  through  this  invasion  of  the  wall  and  of  the  ves- 
sels and  through  an  invasion  of  the  capsularis  by  fetal  cells ;  or, 
since  the  capsularis  does  not  undergo  decidual  change  and  is 
therefore  less  yielding,  the  capsularis  may  rupture.  If  it  be 
torn,  or  if  it  be  not  closely  adherent,  the  intervillous  space  is 
opened.  Abortion,  complete  or  incomplete — usually  incomplete 
—is  the  general  rule,  but  rupture  might  occur.  If  the  abdominal 
end  be  closed  a  hematosalpinx  or  a  tubal  mole  may  represent  the 
final  outcome. 

3.  In  the  centrifugal  form  (Fig.  56a)  the  ovum  sinks  into  the 
wall  of  the  tube  and  an  invasion  of  the  wall  and  vessels  by  the 
villi  may  take  place  even  up  to  the  serosa.  The  capsularis  is 
formed  by  muscularis  and  mucosa.  It  may  rupture  at  its  sum- 
mit. The  invasion  of  the  vessels  entering  the  intervillous  space 
may  cause  hemorrhage.  The  villi  which  extend  up  to  the  serosa 
may  cause  bleeding,  though  their  penetration  is  so  gradual  that 
these  points  are  usually  covered  with  thrombi.  Finally  a  rupture 
may  take  place  at  the  placental  site  through  multiple  perfor- 
ations producing  an  arrosion.  The  ovum  practically  eats  up  the 
wall.  Even  though  the  tubal  diameter  be  large  enough  to  give 
sufficient  room,  this  occurs.  It  is  not  the  result  of  pressure,  as 
may  be  seen  in  gestation  at  the  fimbrian  end,  where  rupture  also 
can  result.  Villi  which  perforate  the  serosa  may  cause  a  very 
decided  hemorrhage  into  the  peritoneal  cavity.  "When  no  rupture 
has  occurred  and  the  abdominal  end  of  the  tube  is  closed, 
only  the  microscope  may  divulge  the  source  of  such  an  in- 
traperitoneal bleeding.  Such  minute  perforations,  may  cause 
collapse  through  hemorrhage,  even  though  the  opening  be  no 
larger  than  the  head  of  a  pin.  Even  after  the  death  of  the  ovum 
the  villi  can  grow,  and  an  active  tubal  mole  is  found  with  con- 
tinued bleeding.  If  they  do  not  grow,  hemorrhage  continues, 
since  no  contraction  can  take  place,  as  is  the  case  in  the  uterus. 
The  centrifugal  form  furnishes  the  majority  of  tubal  ruptures. 
But  the  vast  majority  of  these  so-called  tubal  ruptures  are  either 
erosions  or  due  to  erosion  by  the  perforating  villi. 


CHAPTER  IV. 
THE  USUAL  COURSE  OF  ECTOPIC  GESTATION. 

The  theory  that  the  tube  ruptures  because  the  ovum  is  too  big 
is,  as  a  rule,  wrong  for  cases  in  the  first  three  months.  The 
various  interruptions  of  ectopic  gestation  are  all  the  result  of 
hemorrhages  primarily  minute.  The  usual  ending,  clinically,  of 
the  gestation  begins  with  bleeding  in  the  tube.  The  invasion  of 
the  vessels  of  the  mucosa  and  the  tube  wall  and  the  invasion  of 
the  serosa  furnish  the  causes  for  hemorrhage.  The  death  of  the 
fetus,  as  in  the  case  of  the  uterus,  brings  about  changes  which 
result  in  bleeding.  The  primary  cause  is  a  lack  of  decidua.  In 
a  mucosa  previously  affected,  when  many  large  vessels  are 
changed  by  the  fetal  cells  and  invaded  by  villi,  an  increase  in 
tension  through  contraction  of  the  tube  walls  furnishes  an  easy 
explanation  of  this  hemorrhage.  In  the  uterus  the  vessels  are 
firmly  embedded  in  the  thick  decidua  and  take  a  twisted  course ; 
in  the  tube  the  vessels  are  straight  and  embedded  in  loose  con- 
nective or  fetal  tissue.  Bleeding  on  the  part  of  the  capsule  is 
possible  and  of  frequent  occurrence,  since  it  does  not  undergo 
decidual  change  and  may  be  invaded  by  fetal  cells.  The  con- 
traction of  the  muscle  fibres  on  either  side  of  the  capsularis  ren- 
ders the  rupture  of  this  pseudo-reflexa  easy  because  of  the  ab- 
sence of  decidual  changes,  and  the  point  of  rupture  is  usually  at 
the  summit  of  the  capsularis.  If  the  capsularis  be  composed  of 
tubal  folds  the  intervillous  space  is  easily  involved.  If  the  cap- 
sularis be  composed  of  muscularis  and  mucosa  a  decided  bleeding 
may  result  if  only  the  summit  of  the  capsularis  be  torn. 

Rupture  of  the  tube  almost  always  takes  place  at  the  placental 
site,  which  is  the  seat  of  old  and  new  hemorrhages.  The  hemor- 
rhage and  loosening  of  the  ovum  which  represent  the  clinical  end- 
ing of  these  cases  is  not  the  first  bleeding,  for  older  ones  are 
usually  present.  The  various  processes  depend  upon  the  ovum, 
the  condition  of  the  tube  before  pregnancy,  the  character  of  the 
union  of  the  ovum  with  the  tube,  the  place  of  union,  and  trauma. 
The  reaction  of  the  tube  is  limited  to  the  area  of  the  ovum ;  and 
in  this  we  find  the  main  difference  between  tubal  and  uterine 


138  USUAL  COURSE  OF  ECTOPIC  GESTATION. 

gestation.  The  uterus  undergoes  early  independent  growth,  the 
tube  does  not.  With  the  development  of  the  ovum  the  uterus 
grows  hand  in  hand,  while  in  the  tube  the  ovum  makes  room  for 
itself  and  obtains  its  nourishment  by  the  invasion  of  the  tube 
walls.  It  may  stretch  the  circumference  of  the  tube  so  that  its 
wall,  as  in  the  case  of  Abel,  may  be  reduced  to  a  layer  of  con- 
nective tissue  so  thin  that  rupture  may  result  at  any  point. 

Ampullar  cases  usually  end  -in  abortion,  generally  with  hem- 
atocele. There  is  no  obstruction,  unless  decided  adhesions  are 
present,  and  the  blood  is  generally  poured  out  quickly  into  the 
pelvic  peritoneum  or  into  the  sac  of  Douglas.  Such  an  abortion 
may  be  complete  or  incomplete.  Rupture  in  this  situation  oc- 
curs, but  very  rarely.  The  majority  of  tubal  gestations  are 
situated  in  the  isthmus  tuba?  nearer  the  uterine  end.  In  those 
cases  we  have  (1)  abortion  without  rupture,  complete  or  incom- 
plete, with  bleeding  from  the  abdominal  end  of  the  tube.  Gen- 
erally a  hematocele  is  found  at  the  abdominal  end.  The  tubes 
are  often  so  curved  that  it  is  difficult  for  the  blood  to  make  its 
way  to  the  fimbriae,  and  the  oozing  is  of  a  slow  character.  The 
blood  extends  rarely  more  than  a  very  short  distance  toward  the 
uterine  end,  because  of  the  numerous  short  curves  present  here. 
( 2 )  We  may  have  single  or  multiple  microscopic  perforations  of 
the  tube  wall  by  villi,  causing  even  decided  hemorrhage  without 
apparent  cause.  (3)  We  may  have  macroscopic  perforations  or 
"erosions"  of  the  tube  wall,  covered  or  not  covered  by  thrombi, 
and  causing  great  hemorrhage.  (4)  We  may  have  abortion  with 
rupture  either  into  the  free  abdominal  cavity  with  no  hematocele 
at  the  abdominal  end  of  the  tube,  or  with  partial  encapsulation, 
in  which  event  there  may  be  hematocele  at  the  abdominal  end  if 
the  tube  is  open.  (5)  We  may  have  an  intraligamentous  tear 
with  hematocele  at  the  abdominal  end.  In  these  latter  cases  the 
placental  site  is  always  on  the  inferior  surface  of  the  tube  and 
the  ovum  has  descended  centrifugally  to  the  vessels  of  the  lig- 
amentum  latum.  These  are  by  far  the  most  difficult  cases  surgi- 
cally, and  may  require  hysterectomy  to  remove  the  mass  in  toto. 

Case  I.  (Fig.  47). — Twenty-eight  years  of  age,  married  thir- 
teen years.  One  labor  eleven  years  ago.  Divorced  ten  years 
ago,  and  operated  vaginally  at  Mt.  Sinai  for  pelvic  abscess,  since 
which  time  periodical  attacks  of  pain  on  the  right  side  every 
three  months.  Married  again  twenty  months  ago.  One  year  ago, 
pain,  fainting  spells.  Three  months  before  admission,  pain.  Two 
months  before,  only  stains  instead  of  menstruation.     One  week 


USUAL  COURSE  OF  ECTOPIC  GESTATION.  139 

before,  severe  cramps,  fainting  spells,  following  a  metror- 
rhagia of  several  weeks.  Operation  showed  plenty  of  old  blood  in 
the  pelvic  cavity.  Tube  distended,  clot  at  fimbrian  end.  Other 
tube  normal.  Microscope,  columnar  type,  with  evidences  of  a 
previous  old  ectopic  gestation. 

Case  II.  (Fig.  53). — Twenty-seven  years  old;  four  children, 
last  nine  months  ago.  Nursing.  Four  weeks  of  abdominal 
cramps  and  uterine  hemorrhage.  Well  for  one  week  and  then 
symptoms  returned  up  to  admission,  on  which  day  she  fainted 
three  times  on  account  of  pain. 

Operation.— Much  blood;  right  tube  distended  and  clot  at 
fimbrian  end.  Ovarian  cyst.  Incomplete  tubal  abortion.  In- 
tercolumnar  type,  villi  and  cells  of  Langhans  and  syncytium  in 
the  wall.  Keflexa  consisted  probably  of  folds  involving  one  half 
the  circumference  of  the  tube.  The  other  half  of  the  lumen 
normal. 

Case  III.  (Fig.  56). — Old  blood  clots  in  the  abdominal  cavity 
showed  the  cause  of  the  increasing  attacks  of  pain  with  intervals 
of  relief  to  be  due  to  bleedings  from  perforations  of  the  tube 
wall  which  were  closed  at  times  by  the  formation  of  thrombi. 

Case  IV.— Patient  32  years  old;  two  children,  last  three  years 
ago.  Skipped  two  menstrual  periods.  Two  weeks  later  ex- 
amined because  of  abdominal  pain.  Examination  showed  left- 
sided  tumor,  elastic,  with  pulsating  vessels  on  the  left  side  of  the 
vagina.  Uterus  enlarged.  Next  day  signs  of  hemorrhage,  pale, 
pulse  120. 

Operation  showed  much  blood,  dark  clots,  and  bleeding  from 
the  tubal  end.  Incomplete  tubal  abortion,  placental  mole,  slight 
involvement  of  the  wall.     No  Graafian  follicle  in  the  ovary. 

Case  V. — Twenty-five  years  old;  three  children,  last  fifteen 
months  ago.  Three  months  ago  first  menstruation  (probably 
nursing).  Two  months  ago  skipped  menstrual  period.  For 
four  weeks  metrorrhagia  and  cramps  lasting  fifteen  to  twenty 
minutes  and  recurring  as  often  as  three  to  four  times  a  day. 

Operation.—  Vaginal  celiotomy.  Little  free  blood.  Micro- 
scope. Ovum,  disintegrated  by  blood  and  surrounded  by  villi 
and  tubal  folds,  found  in  the  tube.  Folds  also  present  in  the 
wall  at  many  points.  Organized  clot  adherent  at  one  point. 
Intercolumnar  and  partly  centrifugal,  for  muscularis  and  mucosa 
extend  on  either  side  partly  over  the  mole.  Organized  tubal 
mole.     No  fresh  bleeding. 

Case  VI. — Thirty-seven  years  old;  married  eighteen  years;  six 


140  USUAL  COURSE  OF  ECTOPIC  GESTATION. 

children,  last  three  years  ago.  Last  menstruation  four  months 
ago.  Operated  because  of  abdominal  pains.  No  blood  in  the 
peritoneum.  Tube  and  ovary  free.  Continued  bleeding  into 
the  tube,  which  was  full  of  fresh  blood.  Probably  would  have 
broken  through  the  closed  abdominal  end.  Incomplete  tubal  abor- 
tion of  the  type  of  hematosalpinx.  Placental  mole.  Decided  in- 
volvement of  tubal  wall.  Large  vessel  in  the  periphery  going 
over  gradually  into  the  intervillous  space. 

These  cases,  point  to  the  decided  danger  from  continued  bleed- 
ings involved  in  tubal  abortion.  The  general  view  is  that  tubal 
rupture  gives  much  more  pronounced  symptoms  and  a  much 
more  decided  hemorrhage  than  tubal  abortion.  When  we  con- 
sider that  incomplete  abortion  means  that  villi  are  left  in  the 
tubal  wall  and  that  so-called  complete  tubal  abortion  means  the 
retention  of  trophoblast  cells,  we  may  readily  understand  that 
bleeding  may  continue  for  an  indefinitely  long  period.  It  is  a 
fact,  however,  that  even  complete  abortion  may  cause  decided 
symptoms.  Mandl  reports  two  cases  from  the  clinic  of  Schauta, 
accompanied  by  pronounced  collapse  and  decided  hemorrhage. 
In  the  first  case  no  villi  were  found  in  the  tube  wall  (see 
Fig.  53).  In  the  second  case,  although  villi  were  found  in  the 
blood  clot  in  the  tube,  none  were  found  in  the  tube  wall.  Like 
cases  of  tubal  abortion,  with  symptoms  as  severe  as  are  frequently 
the  rule  with  tubal  rupture,  have  been  reported  by  Klein,  Zedel, 
Piering,  and  others.  It  seems  to  me  these  histological  and  clini- 
cal evidences  are  of  sufficient  weight  to  destroy  the  view,  prevail- 
ing in  many  minds,  that  tubal  rupture  should  be  treated  by  ex- 
tirpation of  the  tube  and  that  tubal  abortion  demands  only  con- 
servative treatment.  The  proportion  of  tubal  abortion  to  tubal 
rupture  is  probably  8  or  10  to  1.  In  this  connection  it  is  quite 
sufficient  to  mention  the  dangers  arising  from  hematocele.  The 
injury  to  the  peritoneum,  the  adhesions  which  take  place,  and 
above  all  the  by  no  means  infrequent  occurrence  of  subsequent 
purulent  degeneration  of  such  an  accumulation  of  blood,  are  only 
some  of  the  injurious  results  avoided  by  prompt  removal. 

The  possibilities  are  represented  by  the  processes  of  abortion, 
microscopic  perforation,  macroscopic  perforation,  rupture,  hema- 
tosalpinx, and  tubal  mole.  In  99  cases  of  interrupted  tubal 
gestation  in  the  clinic  of  Schauta,  a  hematocele  was  found  60 
times — 55  after  abortion,  5  times  after  rupture.  If  the  bleeding- 
be  very  slow,  the  blood  forms  a  capsule  (due  to  peritoneal  ad- 
hesions) into  which  the  subsequent  hemorrhages  enter,  the  so- 


USUAL  COURSE  OF  ECTOPIC  GESTATION.  141 

called  secondary  hematocele.  If  adhesions  are  present  at  the 
abdominal  end  of  the  tube  they  may  form  a  portion  of  the  cap- 
sule. The  resulting  hematocele  after  rapid  bleeding  furnishes 
the  primary  or  diffuse  form.  The  secondary  hematocele  occurs 
much  more  frequently  than  the  primary.  In  the  60  hematoceles 
found  among  99  cases  in  the  clinic  of  Schauta,  only  4  were  dif- 
fuse. Of  the  abortions  found  in  the  same  clinic,  75  were  incom- 
plete and  6  were  complete. 


PART  III. 

OVAKIAN  AND  PLACENTAL  SECRETION. 


THE  RELATION  OF  THE  CHORIONIC  EPITHELIUM  TO 
CHORIO-EPITHELIOMA. 

There  have  been  observed  and  reported  over  150  cases  of  a 
uterine  growth  of  exceedingly  malignant  character  occurring 
after  abortion  and  labor,  or  even  after  tubal  abortion.  The 
clinical  symptoms  are:  (1)  Pronounced  uterine  hemorrhage, 
recurring  even  after  repeated  curettage;  (2)  very  early  metas- 
tases, especially  in  the  lungs  and  vagina;  and  (3)  early  death 
through  hemorrhage,  cachexia,  or  septic  infection. 

Macroscopically,  these  tumors  are  more  or  less  localized,  ul- 
cerating, degenerating,  hemorrhagic  growths,  frequently  passing 
deeply  into  the  uterine  wall,  or  through  it  with  involvement  of  the 
peritoneum. 

Microscopically,  these  tumors  are  characterized  by  hemorrhagic 
areas,  areas  of  degeneration,  the  presence  of  fibrin,  and  the 
involvement  and  invasion  of  capillaries  and  large  vessels.  They 
are  especially  characterized  by  the  presence  of  (1)  pale  round 
and  polygonal  cells  with  pale  protoplasm  and  pale  nucleus,  and 
(2)  of  large  round  and  spindle-shaped  cells  with  large  dark 
nuclei  and  also  (3)  of  large,  irregular  branches  composed  of  poly- 
nuclear  protoplasmatic  masses. 

These  atypical  growths  have  been  variously  described  as  sar- 
coma, carcinoma,  carcinoma  after  abortion  and  labor,  and  as 
sarcoma  and  carcinoma  causing  abortion. 

Sanger,  in  reviewing  these  cases,  found  a  decided  resemblance 
in  their  characteristic  elements,  and  came  to  the  conclusion  that 
the  decidua  cells  were  the  cause  of  the  growth,  giving  it  then 
the  name  of  deciduo-sarcom  or  deciduoma  malignum. 

As  a  result  of  the  investigations  of  Frankel,  and  later  of  Mar- 
chand,  attention  was  called  to  the  fact  that  those  cells  which 
so  closely  resembled  decidua  cells  were  really  of  fetal  origin 
and  were,  in  fact,  the  cells  of  Langlians,  while  the  spindle-shaped 
and  grouped  masses  of  polynuclear  protoplasm  were  of  syncytial 
origin. 

10 


146  RELATION   OF    THE    CHORIONIC    EPITHELIUM 

From  all  sides,  especially  in  England  and  Germany,  this  view- 
was  attacked.  It  was  pointed  out  how  baseless  was  the  view- 
that  fetal  cells  could  produce  a  growth  of  this  malignant  char- 
acter, differing  from  carcinoma  only  in  the  fact  that  metastases 
resulted  through  the  blood  channels  instead  of  the  lymph  paths. 

This  controversy  is  to-day  by  no  means  settled,  many  holding 
the  view  that  these  tumors  are  sarcomatous,  originating  from  the 
decidua  cells.  The  giant  cells  and  the  protoplasmatic  masses 
are  referred,  likewise,  to  changes  in  the  decidua.  Others  hold 
that  these  growths  result  from  the  epithelial  covering  of  the  villi. 
That  these  cells,  if  they  are  of  fetal  origin,  should  be  mistaken 
for  decidua  cells  is  a  natural  error,  for  we  know  that  even  in 
the  normal  processes  a  positive  distinction  is  often  very  difficult. 
It  is  to  be  noted  that  many  investigators  have  called  the  typical 
trophoblast  cells  in  tubal  placentation,  too,  decidua  cells.  Still 
others  lean  to  the  view  that  the  stroma  of  the  villi  plays  its  part. 

On  the  other  hand,  among  those  who  hold  that  these  growths 
originate  from  the  chorionic  covering  a  division  of  sentiment  ex- 
ists ;  for  those  who  consider  the  syncytium  and  cells  of  Langhans 
to  be  of  uterine  origin  class  these  growths  as  carcinoma  and  sar- 
coma of  a  somewhat  atypical  character.  Those  who  believe,  as  we 
have  shown,  that  the  epithelial  covering  of  the  villi  is  of  fetal 
ectodermal  origin,  and  who  therefore  also  class  these  tumors 
under  the  category  of  carcinoma,  are  introducing  into  pathology 
a  new  element. 

A  factor  which  has  served  to  clear  our  views  on  these  various 
disputed  points  is  the  knowledge  that  fifty  per  cent  of  these 
malignant  uterine  growths,  commonly  known  as  deciduoma,  fol- 
low the  presence  of  hydatid  mole. 

In  hydatid  mole  we  find  the  same  elements  as  in  normal  pla- 
centation, only  that  these  elements  are  excessive  in  number  and 
size.  Hydatid  mole  represents  a  hypertrophic  growth  of  the 
chorionic  covering,  accompanied  by  dropsical  swelling  of  the 
chorionic  stroma.  As  is  well  known,  the  covering  of  the  villi 
consists  of  two  layers,  an  outer  syncytium,  an  inner,  the  cell  layer 
of  Langhans.  The  growth  concerns  both  the  syncytium  and  the 
cell  layer  of  Langhans.  The  abnormal  element  is  the  occurrence 
of  very  large  cells  with  immense  nuclei  in  large  number,  and  a 
decided  growth  of  the  syncytium,  accompanied  by  the  forma- 
tion in  the.  latter  of  large  vacuoles. 

Leaving  out  of  consideration  those  cases  malignant  because  of 
the  diffuse  and  deep  infiltration  of  the  uterine  wall  by  the  cystic 


TO    CHORIO-EPITHELIOM.A.  147 

villi,  by  no  means  are  all  hydatid  moles  of  a  malignant  character. 
An  attempt  to  distinguish  between  the  benign  and  malignant 
cases  was  proposed  by  Neumann.  He  observed,  in  three  cases 
subsequently  resulting  in  the  so-called  deciduoma,  large  cell  ele- 
ments in  the  stroma  of  numerous  villi  which  he  considered  to  be 
infiltrating  elements  of  the  syncytium.  He  observed,  further,  an 
abnormal  infiltration  of  cell  groups  through  such  syncytial  ele- 
ments. Investigation  of  subsequent  cases  shows  that  malignant 
forms  are  not  always  preceded  by  such  changes  in  the  hydatid 
mole,  while  others  have  found  these  changes  and  yet  no  malig- 
nant growth  occurred. 

Even  the  occurrence  of  metastases  is  no  proof  of  malignancy, 
for  Pick  reported  a  case  with  a  metastasis  of  villi  in  the  vagina 
and  yet  the  patient  recovered.  We  know  that  fetal  cells  are 
given  off  from  the  normal  placenta  into  the  maternal  circulation. 
Even  the  normal  placenta,  as  Pick  believes,  may  give  metastases 
of  villi,  and  these  may  (1)  degenerate  or  (2)  grow  slightly  or 
(3)  produce  the  same  syncytial  growth  as  is  observed  in  benign 
hydatid  mole.  (4)  Primary  malignant  growths  may  originate, 
and  have  originated,  from  such  metastases. 

Malignancy,  in  the  case  of  hydatid  mole,  is  not  then  to  be 
judged  alone  by  the  occurrence  of  metastases.  Those  cases  which 
subsequently  develop  into  the  so-called  deciduoma  evidence  their 
malignant  character  by  the  ability  of  their  cells  to  grow  in  an 
unlimited  manner,  aided  by  the  character  of  the  tissue  which  per- 
mits or  also  aids  this  growth.  Various  theories  have  been  pro- 
pounded in  explanation  of  this,  phenomenon.  1.  Through  the 
syncytium  there  is  a  constant  exchange  of  products,  and  after 
hydatid  mole,  or  on  the  occurrence  of  abortion  or  labor  or  any 
process  causing  the  removal  or  death  of  the  fetus,  this  exchange 
ceases.  The  fetal  cells  then,  if  in  a  favorable  surrounding,  are 
supposed  to  use  this  nutrition  for  themselves  and  increase  until 
an  unlimited  growth  results  (theory  of  Marchand).  2.  Ribbert 
considers  the  unlimited  ability  of  certain  malignant  tissues  to 
grow  to  be  due  to  the  separation  of  their  mother  cells  from  their 
normal  connections.  3.  As  is  well  known,  Cohnheim  considered 
displaced  embryonal  cells  to  be  the  future  source  of  many  Benign 
and  malignant  tumors. 

An  interesting  power  or  potential  retained  by  displaced  cells 
is  that  of  differentiation.  We  know  that  displaced  cells,  cells  re- 
moved from  their  normal  relations,  are  able,  after  an  interval  of 
many  years,  to  grow  and  produce  structures  of  varying  form. 


148  RELATION    OF    THE    CHORIONIC   EPITHELIUM 

This  is  best  exemplified  in  the  case  of  dermoid  cysts,  for  their 
character  distinguishes  them  from  all  other  tumors.  The  later 
in  the  stage  of  embryonal  development  these  cells  are  displaced 
the  more  simple  is  the  structure  of  the  resulting  dermoid;  the 
earlier  in  the  period  of  embryonal  development  their  displacement 
occurs  the  less  differentiated  are  these  cells.  For  that  reason 
embryonal  cells  displaced  in  the  early  weeks  produce  tumors  of 
complicated  character,  for  their  potential  as  regards  differentia- 
tion is  great.  Cells  displaced  at  a  later  period  possess  a  lesser 
potential  as  regards  differentiation,  while  those  epithelial  and 
connective-tissue  cells  displaced  very  late,  as  at  points  where  the 
skin  only  remains,  to  be  united,  and  at  the  branchial  clefts,  pro- 
duce only  the  simplest  form  of  dermoid  growth.  They  produce 
only  cells  of  the  same  character  and  structure  as  the  parent  cell 
if  the  stage  of  complete  differentiation  had  been  already  reached. 
If  the  displacement  occurs  before  this  period,  such  elements  are 
found  in  the  subsequent  growth  as  the  parent  cells  would  have 
produced  had  they  remained  in  their  normal  situation.  Such 
early  cells,  however,  reproduce  far  greater  growths  and  far  more 
extensive  tissues  than  would  have  resulted  had  they  not  been  dis- 
placed. This  is  evidenced  by  the  fact  that  no  loss  of  any  normal 
tissue  or  structure  results.  In  dermoid  cysts  of  the  ovary,  for 
instance,  very  large  and  complicated  tumors  are  found,  resulting 
from  the  displacement  of  ectodermal  and  mesodermal  cells  by  the 
Wolffian  body,  and  yet  the  maternal  body  is  otherwise  normally 
developed. 

In  the  genital  tract,  especially,  we  find  numerous  evidences  of 
another  cell  potential,  that  is,  the  ability  to  first  display  ac- 
celerated growth  after  a  lapse  of  many  years.  We  find  in  the 
uterine  wall,  under  the  peritoneum,  in  the  broad  ligament,  and 
in  the  ovary,  generally  after  puberty,  epithelial  and  glandular 
growths,  sometimes  of  considerable  size,  resulting  from  the  dis- 
placement of  cells  of  the  Wolffian  body.  In  the  fetus  and  in  the 
newly-born,  hundreds  of  uteri  and  appendages  have  been  ex- 
amined and  yet  relatively  few  such  displacements  of  Wolffian- 
body, cells  can  be  found.  This  means  that  the  displacement  con- 
cerns simply  embryonal  cells  of  this  organ,  which  even  at  a  much 
later  period  possess  the  power  to  develop  the  same  structures  as 
the  parent  organ.  This  growth  takes  place,  as  a  rule,  at  and 
after  puberty,  and  the  same  is  true  in  the  case  of  dermoid  cysts. 

We  find,  then,  that  the  general  stimulation  of  tissue  and  cell 


TO    CHORIO-EPITHELIOMA.  149 

growth  occurring  after  puberty  may  influence  some  embryogically 
displaced  cells  in  the  same  manner. 

We  find,  on  close  investigation,  that  almost  all  ovarian  and 
parovarian  cysts  result  from  the  continued  growth  of  structures 
which  in  the  embryo  were  functionating  organs',  but  which  in  the 
fetus  and  in  the  adult  are  supposed  to  undergo  regressive 
changes,  namely,  the  epoophoron  and  the  paroophoron,  con- 
stituting the  two  divisions  of  the  Wolffian  body.  Papillomata  of 
the  ovary,  in  all  probability,  also  develop  from  cells,  of  these  sup- 
posedly regressive  structures.  Ovarian  cysts  also  frequently 
show  papillomatous  changes.  These  are,  strictly  speaking, 
only  huge  increases  of  the  characteristics  of  the  primary  embry- 
onal organ. 

Not  infrequently  these  papillomatous  growths  are  macroscopi- 
cally  of  a  malignant  character,  in  that  they  break  through  the 
covering  of  the  cyst  or  through  the  ovary,  grow  without  restric- 
tion, invade  the  peritoneum,  infiltrate  the  surrounding  organs, 
and  produce  cachexia. 

Such  changes  may  also  display  the  microscopic  characteristics 
which  we  attribute  to  carcinoma— that  is,  a  continued  growth  of 
the  epithelium,  a  breaking  through  of  the  membrana  propria, 
and  an  infiltration,  microscopically,  of  the  tissue  surrounding  the 
epithelial  cells.  In  other  words,  we  find  a  continued  unlimited 
growth  of  cells,  reproducing,  even  though  in  a  changed  relation, 
the  character  of  the  mother  cell. 

These  smaller  and  larger  reproductions  of  the  Wolffian  body, 
these  cystic  growths  originating  from  the  Wolffian-body  cells, 
these  papillary  and  malignant  growths  originating  from  the  same 
source,  as  well  as  dermoid  cysts,  furnish  us  with  evidence  of  the 
ability  of  regressive  cells  and  organs,  and  cells  removed  from 
their  normal  relations,  to  undergo  a  more  or  less  unlimited 
growth,  even  after  lying  dormant  for  many  years.  These  cells, 
however,  are  cells  of  the  patient  and  are  open  to  the  same  in- 
fluences as  normally  situated  cells. 

In  the  case  of  chorio-epithelioma,  however,  we  find  fetal 
cells,  often  only  a  few  weeks  old,  possessing  naturally  no 
great  potential  as  regards  differentiation,  but  an  exceedingly 
high  potential  as  regards  their  ability  to  grow.  The  energy  and 
potential  of  these  cells  may  be  appreciated  from  the  fact  that  the 
earliest  case  occurred  two  weeks  after  the  interruption  of  preg- 
nancy, while  the  latest  occurred  nearly  four  years  after  hydatid 
mole. 


150  RELATION    OF    THE    CHORIONIC   EPITHELIUM 

The  most  prominent  point  of  a  ripening  Graafian  follicle  is 
poor  in  blood  supply  and  is  called  the  stigma  folliculi.  It  is 
here  that  the  opening  takes  place  which  furnishes  an  outlet  for 
the  ovum.  This  opening  is  probably  the  result  of  the  reaction  or 
chemical  effect  produced  by  the  ripe  ovum,  for,  in  the  newly-born 
and  in  children,  follicles,  of  the  same  size  and  even  larger  ones 
exist  without  bursting— the  so-called  atresic  follicles. 

After  ovulation  the  ovum  is  thrown  out  into  the  abdominal 
cavity,  and  then,  influenced  by  the  wave  movement  of  the  ciliated 
epithelium  of  the  tube,  the  fimbria?  of  the  ampulla,  and  the  fim- 
bria; ovaricae,  finds  its  way  into  the  uterus.  The  wave  movement 
of  the  ciliated  epithelium  causes  a  current  in  the  peritoneal 
plasma  which  directs  the  ovum  into  one  or  other  of  the  tubes. 

A  fecundated  ovum  embeds  itself  in  the  lining  of  the  uterus 
through  centrifugal  descent.  The  ovum  then  causes  a  reaction  in 
the  surrounding  tissue  and  a  dilatation  of  the  surrounding  lymph 
spaces,  so  that  a  resulting  localized  edema  takes  place.  In  addi- 
tion a  dilatation  of  the  capillaries  is  produced. 

The  outer  layer  of  the  ovum  develops  into  what  is  known  as  the 
trophoblast,  which  is  a  product  of  the  ectoderm,  and  from  it 
develop  the  cells  of  Langhans  and  the  syncytium. 

Shortly  after  the  ovum  is  embedded  in  the  mucosa  a  connection 
between  the  trophoblast  and  the  maternal  blood  takes  place 
through  a  rupture  of  the  capillaries.  The  maternal  blood  then 
bathes  the  ectodermal  trophoblast.  This,  opening  of  the  maternal 
vessels  occurs,  however,  before  the  formation  of  villi;  and  the 
cells  of  the  trophoblast  may  therefore  enter  the  maternal  veins 
at  the  very  earliest  period. 

The  compact  layer  of  the  decidua  is  the  zone  which  envelops 
the  ovum.  The  trophoblast  at  points  may  extend  far  into  the 
compacta,  for  the  cells  have  a  decided  poiver  of  wandering.  The 
trophoblast,  therefore,  invades  the  maternal  tissues  even  at  the 
earliest  period. 

A  gradual  transition  of  trophoblast  cells  into  syncytial  cells, 
and  a  gradual  change  of  trophoblast  nuclei  to  syncytial  nuclei, 
take  place  through  the  corrosive  action  of  the  maternal  blood, 
and  elements  of  the  maternal  blood  aid  in  forming  the  syncytial 
protoplasm.  The  syncytium  does  not  originate  from  the  ma- 
ternal endothelium,  nor  from  the  uterine  epithelium,  nor  from 
the  decidua  cells. 

Just  as,  in  the  early  stages,  the  trophoblast  invades  the  de- 
cidua, so,  after  the  formation  of  villi,  is  the  future  course  of  the 


TO    CHORIO-EPITHELIOMA.  151 

ectodermal  trophoblast  and  of  the  syncytial  cells  of  a  destructive 
character  so  far  as  the  decidua  is  concerned.  The  trophoblast  and 
syncytium  invade  the  maternal  tissue  and  mingle  with  it.  They 
infiltrate  the  decidua  and  bring  it  to  destruction.  The  tropho- 
blast and  syncytial  cells  erode  the  capillaries  and  blood  vessels, 
the  blood  in  turn  changing  fetal  cells  to  syncytium. 

The  invading  trophoblast  and  syncytial  cells  have  at  all  times 
a  great  power  of  wandering.  They  enter,  between  bundles  of 
muscular  and  connective  tissue,  into  the  lymph  spaces  and  into 
the  blood  vessels.  At  full  term  the  uterine  wall  is  infiltrated  with 
fetal  cells  of  a  syncytial  character. 

From  the  very  earliest  moment  fetal  cells  are  continually  enter- 
ing the  blood  of  the  mother,  not  only  in  the  primary  intervillous 
space  but  in  the  fully  formed  intervillous  space,  as  well  as 
through  the  vessels  of  the  uterine  decidua  and  wall. 

CHORIO-EPITHELIOMA. 

Under  chorio-epithelioma  we  distinguish  two  forms,  the  typical 
and  atypical.  In  the  typical  form  (Fig.  60)  we  find  large,  round, 
polyhedral  cells  with  strikingly  large,  very  irregular,  lobulated 
nuclei  which  stain  very  deeply  and  often  degenerate,  forming 
vacuoles.  The  protoplasm  is  relatively  scanty.  These  cells  are 
capable  of  great  wandering  and  are  found  more  or  less  isolated 
between  the  muscle  and  the  connective-tissue  bundles  (Fig.  63), 
in  the  lymph  spaces  and  in  the  vessels.  They  form  the  advance 
guard  in  the  way  of  infiltration.  There  are,  further,  irregular 
bridges  of  protoplasm  containing  scattered  or  grouped  nuclei  of 
various  sizes  (Fig.  61).  Many  of  these  groups  of  nuclei  are  the 
same  large,  irregular,  lobulated  nuclei  as  were  observed  in  the 
form  just  mentioned.  In  addition  are  found  irregular  masses  of 
protoplasm  containing  many  small  nuclei.  The  character  of  the 
latter  is  identical  with  normal  syncytium. 

The  irregular  groups  of  protoplasm  containing  grouped  nuclei 
of  various  sizes  are  undoubtedly  of  syncytial  character,  for  they 
result  through  the  blood  surrounding  and  infiltrating  the  cells 
of  Langhans,  and  it  is  very  evident  that  these  cells  form  the  afore- 
mentioned grape-like  nuclei  (Fig.  63).  The  isolated  large  cells 
are  likewise  of  syncytial  character.  They  have  generally  been 
mistaken  for  decidua  cells.  They  may  be  distinguished  from  the 
cells  of  Langhans,  for  the  latter  are  pale,  polyhedral  groups  of 
distinctly  epithelial  character.  They  are  rich  in  glycogen  and 
therefore  often  contain  vacuoles.     The  nuclei  are  large  but  pale. 


152 


RELATION    OP    THE    CHORIONIC    EPITHELIUM 


The  cells  of  Langhans  are  better  illustrated  in  the  atypical 
form  (Fig.  64)  where  the  syncytial  elements  are  relatively  in  the 
background.  In  fact,  no  more  and  no  different  syncytial  cells  are 
present  here  than  in  normal  gestation.  The  trophoblast  cells  lie 
closely  grouped  and  are  surrounded  by  syncytial  elements  in 

s 


Syncytium 


Large 

syncytial 

cell 


=0  8  5s  <" 


..      «  5>  t.  „°  5vS        S> 

r-H    H  Co  Citii  CO  Ca         BQ 


Vt.  tissue 

Syncytium 
icitli  large 
vacuoles 
Syncytial 
mass 


WTtS&M 


I 


Vt.  tissue 


X„ 


Large  syncytial  cells 
with  large  nuclei 


Fig.  60. — Low-power  drawing  of  the  typical  form  of  chorio-epithelioma,  show- 
ing the  uterine  wall  invaded  by  chorionic  elements.  X,  X,  X,  three  areas  of  dense 
connective  tissue  surrounded  by  chorionic  epithelial  elements  and  resembling 
chorionic  villi.  Y,  connective  tissue  centre  surrounded  by  polynuclear  syncytial 
mass  of  considerable  thickness,  probably  a  villus. 


quite  the  same  manner  as  in  normal  gestation,  or  especially  in 
tubal  gestation.  They  are  polygonal  cells,  concerning  which 
different  views  have  been  held.  They  have  been  called  decidua 
cells.  No  vessels  of  their  own,  however,  are  present  in  these 
epithelial-like  groups,  and  their  character,  their  structure,  and 
their  arrangement  so  closely  resemble  the  trophoblast  cells  ob- 
served in  normal  gestation  that  any  other  view  is  not  to  be  con- 


TO    CHORIO-EPITHELIOM A . 


153 


sidered.     These  epithelial-like  cells  and  the  syncytial  masses  of 
various  forms  all  originate  from  the  trophoblast  cells. 

In  these  growths  newly  formed  villi  have  not  yet  been  found  — 
a  proof  of  the  limited  power  of  differentiation  possessed  by  the 

Syncytial  strand 


.     ,.^-. 


.-.-■— ■or' 


*£*V*.>* 


,..-,■ 


•  -;     •  *  .~*V  :^«,.  ,..- ..-. ■■■< 

Fig.  61. — Upper  left-hand  corner  of  Fig.  60  highly  magnified,  showing  the 
character  of  the  polynuclear  syncytial  masses.  Along  the  right  and  lower  bor- 
ders are  larger  isolated  mononuclear  syncytial  cells. 


trophoblast  cells  alone.  It  may  be  said,  therefore,  that  two  forms 
of  this  tumor  exist,  the  first  typical,  the  second  atypical.  The  for- 
mer cases  are  so  characteristic  that  they  cannot  be  mistaken.  The 
latter  have  been  so  frequently  called  carcinoma  by  eminent  an- 


154 


RELATION    OF    THE    CHORIONIC    EPITHELIUM 


thorities  that  our  belief  that  many  of  these  are  overlooked  and 
incorrectly  diagnosed  is  certainly  true. 

A  study  of  the  histology  of  so-called  deciduomata,  and  a  com- 
parison of  their  structure  with  the  structure  of  normal  placental 
elements,  prove  these  tumors  to  be  of  fetal  origin.  The  cells 
from  which  they  develop  are  the  cells  which  cover  the  chorionic 
villi.  Since  these  are  epithelial  in  character,  these  tumors,  be- 
longing as  they  do  to  the  most  malignant  forms,  should  be  called 
chorio-epithelioma. 

We  have,  then,  in  the  chorio-epitheliomata  a  reproduction  of 


Syncytial 
strand 


&\     : 


TrophoMast  cells  forming  syncytial  masses 
Blood  and  olood  cells 

Fig.  62. — Highly  magnified  area  of  Fig.  61,  showing  finer  characteristics  of 
syncytial  masses.  Change  of  trophoblast  cells  en  masse  into  polynuclear,  vac- 
uolar structures. 


the  same  constituent  elements  as  are  found  in  normal  placenta tion 
and  as  are  observed  in  benign  and  malignant  cases  of  hydatid  mole. 
These  cells  exert  the  same  influence  and  effect  on  the  maternal 
tissues  as  do  the  fetal  cells  in  a  normal  uninterrupted  pregnancy. 
They  invade,  as  do  the  normal  trophoblast  cells,  the  maternal  de- 
cidua  and  destroy  it.  They  infiltrate  and  erode  the  walls  of  the 
vessels.  They  invade  and  infiltrate  deeply,  too,  the  uterine  wall. 
They  advance  either  as,  distinct  Langhans  or  trophoblast  cells  or 


TO    CHORIOEPITHELIOM.A.  155 

as  syncytial  cells,  or  else  they  undergo  in  their  advance  a  change 
from  the  former  to  the  latter,  especially  when  in  contact  with 
maternal  blood,  as  in  the  case  of  placentation  either  uterine  or 
tubal.  Their  invasion  of  the  maternal  vessels  and  capillaries 
gives  them,  from  their  earliest  existence  as  malignant  cells,  the 
opportunity  of  invading  the  maternal  circulation  with  a  resulting 
early  formation  of  metastases.  Their  ability  to  erode  the  vessels 
causes  profuse  and  constant  bleeding.  Their  ability  to  destroy 
the  maternal  tissue  as  they  advance  produces  larger  and  smaller 
areas  of  degeneration  and  necrosis  accompanied  by  the  presence 
of  much  fibrin.     These  cells  preserve  their  ability  to  grow  when 


TrophoMast 
cell 

Giant  cell 


Giant  cell 

with  granular 

nucleus 


Tit.  tissue 


Fig.  63. — Highly  magnified  area  of  Fig.  60,  showing  character  of  isolated 
mononuclear  giant  syncytial  cells  and  the  infiltration  by  them  of  the  uterine  tis- 
sue and  lymph  spaces. 

they  reach  their  new  locations,  with  the  result  that  they  produce 
in  the  various  organs,  but  most  frequently  in  the  vagina,  malig- 
nant nodules  of  the  same  character  as  the  parent  growth.  In 
fact,  these  secondary  nodules  have  in  some  cases  been  observed 
before  the  character  of  the  uterine  symptoms  called  attention  to 
the  presence  of  malignant  conditions,  in  the  uterus. 

The  fetal  cells  producing  a  chorioma  are  situated  in  the  most 
favorable  surrounding.  They  have  been  performing  practically 
malignant  functions  in  that  they  have  destroyed,  even  during 
normal  placentation,  maternal  tissues,  and  have  invaded  maternal 
vessels,  and  have  been  carried  off  into  the  maternal  circulation. 


156 


RELATION    OF    THE    CHORIONIC    EPITHELIUM 


When  connected  as  part  and  parcel  of  an  ovum,  when  feeding 
and  nourishing  the  fetus  with  the  products  of  the  maternal  blood 
which  have  passed  through  them,  they  are,  so  to  speak,  under 
control  of  the  parent  organism  the  ovum,  yet  when  released  from 
this  connection  they  continue  an  independent  growth  of  their 
own.  It  is  quite  probable  that  in  hydatid  mole  the  edematous 
swelling  of  the  chorionic  stroma  is  due  to  interference  with  the 
proper  exchange  between  the  fetus  and  the  mother,  due  to  a  more 
or  less  increased  and  independent  growth  on  the  part  of  those 
cells  whose  function  it  is,  normally,  to  aid  and  permit  of  this 
exchange.    It  is  likewise  probable  that  the  growth  of  the  chorionic 


Pale 

epithelioid 

cells 


.    Trophoblast 

cells 


Island  of  cells 

_  Syncytial 
veils 


Pig.  64. — High-power  drawing  of  atypical  chorio-epithelioma  greatly  resernblins 
carcinoma. 


cells  in  chorio-epithelioma  takes  place  during  the  pregnancy  and 
is  rather  the  cause  than  the  result  of  abortion. 

We  have  observed  in  the  development  and  change  of  tropho- 
blast cells  to  syncytium  that  the  closely  grouped  cells,  when 
vascularized,  change  to  plasmodial  or  syncytial  cells.  That  the 
blood  of  the  mother  furnishes  the  greater  portion  of  the  proto- 
plasm of  these  syncytial  cells  has  been  clearly  shown.  Therefore 
their  production  and  growth,  even  in  normal  conditions,  depends 
upon  their  taking  up  from  the  mother  essential  elements,  while 
the  trophoblast  cells  themselves  furnish  the  nuclei.  Therefore 
the  growth  of  so  pathological  a  tumor  as  a  chorio-epithelioma  is 
not  absolutely  a  reproduction  of  fetal  cells,  but  is  in  a  more  or 
less  direct  manner  a  maternal  production  also. 


TO   CHORIO-EPITHELIOMA.  1  57 

The  invasion  and  destruction  of  maternal  tissues  in  normal 
gestation  occurs  within  certain  fixed  limits,  and  the  fetal  cells 
entering  the  maternal  circulation  undergo  no  future  growth. 
What  preserves  this  balance?  What  limits  and  controls  the 
potential  of  the  parasitic  fetal  cells?  In  hydatid  mole,  and 
especially  in  chorio-epithelioma,  the  fetal  cells,  are  no  longer  held 
in  check  and  they  possess  the  power  of  unlimited  growth.  What 
has  upset  the  normal  balance  ? 

When  the  fecundated  ovum  enters  the  uterus,  it  destroys  the 
surface  epithelium  under  it  and  descends  actively  into  the  de- 
cidua.  It  produces  a  decided  reaction  in  its  immediate  circum- 
ference, so  that  even  in  its  earliest  stages  it  evidences  a  chemical 
power.  When  the  maternal  blood  makes  its  exit  from  the  capil- 
laries it  ought  to  coagulate,  but  does  not.  It  circulates  against 
the  fetal  cells  which  have  the  power  to  prevent  coagulation. 
The  trophoblast  and  syncytial  cells  are  bathed  by  maternal  blood 
and  enter  the  circulation;  therefore  the  ovum  has  a  certain 
enzyme  action  and  the  fetal  cells  may  be  said  to  furnish  or  repre- 
sent a  placental  secretion. 

On  the  other  hand,  the  blood  contains  elements  which  exert  a 
corrosive  action  on  the  trophoblast  cells,  changing  them  to  syncy- 
tium. The  resulting  syncytial  cells  then  cover  the  villi;  they 
play  the  part  of  endothelium  (which  they  then  greatly  resemble) 
and  protect  the  cells  of  Langhans  and  the  stroma  from  the  corro- 
sive influence  of  the  blood.  That  the  individual  cells  in  chorio- 
epithelioma  have  the  power  to  grow  without  limit,  and  that  the 
cells  entering  the  circulation  have  the  energy  to  produce  malig- 
nant metastases,  shows  that  the  decidua  and  the  blood  no  longer 
have  the  power  to  limit  and  control  their  growth. 

In  reviewing  the  anatomical  and  physiological  characteristics 
of  the  female  sex  before  and  during  pregnancy,  and  bearing  in 
mind  the  normal  changes  of  pregnancy  (such  as  the  cessation  of 
menstruation,  the  act  of  labor,  etc.),  but  especially  the  pathologi- 
cal states  occurring  almost  entirely  or  exclusively  in  connection 
with  pregnancy  (such  as  osteomalacia,  eclampsia,  and  chorio- 
epithelioma),  we  are  forced  to  the  conclusion  which,  while  partly 
theoretical,  is  nevertheless  logical. 

Ovarian  secretion  has  a  great  trophic  influence  upon  the  uterus. 
It  stimulates  the  growth  of  the  round  cells  of  the  stroma  into 
decidua  cells.  The  lining  of  the  uterus  is  truly  a  lymphoid  tissue, 
and  it  is  the  great  development  of  the  decidua  and  its  secretion 
which  prevents  the  involvement  and  macroscopical  perforation  of 


158  RELATION    OP    THE    CHORIONIC    EPITHELIUM 

the  uterine  wall  by  the  placental  villi.  Although  it  may  be  said 
that  ovarian  secretion  stimulates  the  growth  of  the  fetal  cells 
and  that  certain  elements  in  the  blood  hold  their  growth  in  check, 
it  is  probably  the  ovarian  secretion  in  the  maternal  blood  which 
aids  the  decidua  in  holding  the  placental  development  within 
normal  limits,  and  which  renders  the  trophoblast  cells  and  the 
syncytial  cells  entering  the  circulation  innocuous. 

In  normal  placentation  the  human  organism  furnishes  us  with 
a  process  parallel  to  that  occurring  in  certain  bacterial  infections, 
that  is,  the  production  of  two  opposing  toxins  or  ferments :  (1)  a 
blood  element,  probably  the  ovarian  secretion,  and  (2)  the  pla- 
cental secretion. 

In  the  normal  woman  the  ovary  is  responsible  for  the  periodi- 
cal loss  of  blood  known  as.  menstruation.  This  process  is  due  to  a 
secretion  furnished  by  the  ovaries,  for  on  their  removal  this  pro- 
cess ceases  and  the  reduction  of  oxygen  exchange  amounts  to 
twenty  per  cent.  This  secretion  stimulates  various  functions,  of 
the  body,  and  at  regular  periods  an  outlet  for  this  secretion  oc- 
curs. Every  menstruation  represents,  in  addition,  the  birth  of  a 
non-fecundated  ovum,  that  is,  a  labor  en  miniature. 

When,  however,  fecundation  and  development  of  the  ovum 
take  place,  the  ovum  and  its  enzymes  nullify  the  menstrual 
stimulation  of  the  ovarian  secretion.  The  trophoblast  cells  in- 
vade the  maternal  decidua  which  is  stimulated  by  the  ovarian 
secretion,  and  likewise  enter  the  blood  of  the  mother.  A  normal 
gestation  is  accompanied  by  the  stimulating  effects  of  the  retained 
ovarian  secretion  and  these  two  enzymes  are  then  opposed  in  their 
action.  No  menstruation  occurs,  for  the  placental  secretion  has 
nullified  the  action  of  the  usual  forces. 

At  the  end  of  nine  months,  when  the  ovarian  secretion  is  suf- 
ficient in  amount  or  character  to  overcome  the  neutralizing  action 
of  the  enzymes  of  the  ovum,  labor  occurs,  that  is,  the  same  pro- 
cess as  is  observed  in  a  minuter  degree  in  menstruation,  for 
menstruation,  as  said  before,  is  a  labor  en  miniature. 

Remembering  the  constitutional  action  of  ovarian  secretion,  it- 
may  be  said  that  if,  shortly  before,  during,  or  after  labor,  there 
is  an  overwhelming  superiority  of  the  ovarian  secretion  over  the 
placental  or  an  opposite  mal-relation  between  ovarian  and  pla- 
cental secretion,  the  constitutional  involvement  known  as  eclamp- 
sia results. 

Following  the  analogy  further,  it  may  be  said  that  chorio- 
epithelioma  is  due  to  the  fact  that  the  resistance  to  the  fetal  en- 


TO    CHORIO-EPITHELIOMA.  159 

zymes  and  fetal  cells  offered  by  the  blood  and  the  ovarian  secre- 
tion is  insufficient  to  hold  the  growth  of  the  fetal  cells  in  check. 
Chorio-epithelioma  occurring  generally  after  abortion  or  hydatid 
mole  is  certainly  the  cause  rather  than  the  result  of  the  abortion. 
Chorio-epithelioma  represents  a  more  advanced  stage  than  that 
of  hydatid  mole,  but  both  of  these  conditions  follow  the  normal 
processes  in  their  course  and  growth.  The  only  difference  is  the 
power  of  unlimited  growth  possessed  by  the  chorionic  cells  in 
these  pathological  conditions.  The  difference  in  the  resistance 
offered  by  the  patient  points  to  a  constitutional  element  as  an 
important  factor  in  the  etiology  of  chorio-epithelioma. 


^T065280 

BORROWER. 


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